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The dataset generation failed because of a cast error

Error code:   DatasetGenerationCastError
Exception:    DatasetGenerationCastError
Message:      An error occurred while generating the dataset

All the data files must have the same columns, but at some point there are 15 new columns ({'summary', 'pub_date', 'comments', 'hgnc_gene', 'summary_comments', 'entry_index', 'mondo_id', 'assertion', 'evidence_code', 'mode_inheritance', 'disease', 'path', 'expert_panel', 'variant', 'met_status'}) and 9 missing columns ({'Reason for Changed Score', 'Score Status', 'Points (default points)', 'Explanation', 'url', 'Experimental Category', 'primary_index', 'Reference', 'Label'}).

This happened while the csv dataset builder was generating data using

hf://datasets/owencqueen/cgbench_data/VCI/split_evidence_score/train.csv (at revision 34fd1179dc7eda9709d682704d00935c0dccac67)

Please either edit the data files to have matching columns, or separate them into different configurations (see docs at https://hf.co/docs/hub/datasets-manual-configuration#multiple-configurations)
Traceback:    Traceback (most recent call last):
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1871, in _prepare_split_single
                  writer.write_table(table)
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/arrow_writer.py", line 643, in write_table
                  pa_table = table_cast(pa_table, self._schema)
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/table.py", line 2293, in table_cast
                  return cast_table_to_schema(table, schema)
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/table.py", line 2241, in cast_table_to_schema
                  raise CastError(
              datasets.table.CastError: Couldn't cast
              entry_index: int64
              variant: string
              hgnc_gene: string
              disease: string
              mondo_id: string
              assertion: string
              mode_inheritance: string
              expert_panel: string
              pub_date: string
              evidence_code: string
              met_status: string
              pmid: string
              comments: string
              summary: string
              summary_comments: string
              path: string
              -- schema metadata --
              pandas: '{"index_columns": [{"kind": "range", "name": null, "start": 0, "' + 2155
              to
              {'Label': Value(dtype='string', id=None), 'Experimental Category': Value(dtype='string', id=None), 'Reference': Value(dtype='string', id=None), 'Explanation': Value(dtype='string', id=None), 'Score Status': Value(dtype='string', id=None), 'Points (default points)': Value(dtype='string', id=None), 'Reason for Changed Score': Value(dtype='string', id=None), 'url': Value(dtype='string', id=None), 'primary_index': Value(dtype='int64', id=None), 'pmid': Value(dtype='string', id=None)}
              because column names don't match
              
              During handling of the above exception, another exception occurred:
              
              Traceback (most recent call last):
                File "/src/services/worker/src/worker/job_runners/config/parquet_and_info.py", line 1433, in compute_config_parquet_and_info_response
                  parquet_operations = convert_to_parquet(builder)
                File "/src/services/worker/src/worker/job_runners/config/parquet_and_info.py", line 1050, in convert_to_parquet
                  builder.download_and_prepare(
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 925, in download_and_prepare
                  self._download_and_prepare(
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1001, in _download_and_prepare
                  self._prepare_split(split_generator, **prepare_split_kwargs)
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1742, in _prepare_split
                  for job_id, done, content in self._prepare_split_single(
                File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1873, in _prepare_split_single
                  raise DatasetGenerationCastError.from_cast_error(
              datasets.exceptions.DatasetGenerationCastError: An error occurred while generating the dataset
              
              All the data files must have the same columns, but at some point there are 15 new columns ({'summary', 'pub_date', 'comments', 'hgnc_gene', 'summary_comments', 'entry_index', 'mondo_id', 'assertion', 'evidence_code', 'mode_inheritance', 'disease', 'path', 'expert_panel', 'variant', 'met_status'}) and 9 missing columns ({'Reason for Changed Score', 'Score Status', 'Points (default points)', 'Explanation', 'url', 'Experimental Category', 'primary_index', 'Reference', 'Label'}).
              
              This happened while the csv dataset builder was generating data using
              
              hf://datasets/owencqueen/cgbench_data/VCI/split_evidence_score/train.csv (at revision 34fd1179dc7eda9709d682704d00935c0dccac67)
              
              Please either edit the data files to have matching columns, or separate them into different configurations (see docs at https://hf.co/docs/hub/datasets-manual-configuration#multiple-configurations)

Need help to make the dataset viewer work? Make sure to review how to configure the dataset viewer, and open a discussion for direct support.

Label string	Experimental Category string	Reference string	Explanation string	Score Status string	Points (default points) string	Reason for Changed Score string	url string	primary_index int64	pmid string
Yoshimura_Expression	Expression A	Yoshimura H, et al., 2014, PMID: 24676347	Investigation of differential expression of many genes in the mouse cochlea between apical, middle, and basal turns revealed that CRYM expression was higher in the apex than in the base.	Score	0.25 (0.5)	0.25 points given because no explanation of relevance to CRYM hearing loss is provided	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_d15cf48a-3696-467a-b3c8-a45ef5a577bf-2021-09-21T160000.000Z	534	PubMed:24676347
Northern and Western Blot	Expression A	Faulkner G, et al., 1999, PMID: 10427098	Northern blot analysis revealed LDB3 is expressed in the heart and skeletal muscle. Western blot analysis was also consistent with this finding.	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7756e3c0-5a16-49b8-ac0f-220e79a4fa99-2020-09-25T160000.000Z	1,194	PubMed:10427098
crystal structure of BMP9:ALK1 complex at 3.3 Å	Protein Interaction	Salmon RM, et al., 2020, PMID: 32238803	ALk1 variants have been found in a number of probands with hereditary hemorrhagic telangiectasia. ALK1-mediated endothelial BMP9 and BMP10 signaling plays many important roles in angiogenesis and the maintenance of vascular quiescence. This paper demonstrated that the BMP9 GF-domain binds to the extra cellular domain o...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_00608fb7-3483-495a-8f9e-76aabb4b1dc0-2023-04-03T160000.000Z	879	PubMed:32238803
Taok1 knock-down embryonic mouse brain	Model Systems Non-human model organism	van Woerden GM, et al., 2021, PMID: 33565190	Reduced Taok1 expression levels in the embryonic mouse brain affect neural migration in vivo, a process that is critical for normal brain development.	Score	1.5 (2)	Because TAOK1 role in neuronal migration was scored in other experimental evidences included in this curation, evidence from this model system was lowered to prevent scoring the same evidence twice.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_79c712d0-ac0e-4bf0-8e68-bd598b3bca42-2021-08-04T160000.000Z	2,130	PubMed:33565190
COL6A1 Spontaneous Canine Model	Model Systems Non-human model organism	Steffen F, et al., 2015, PMID: 26438297	This naturally occurring model of Collagen VI-related myopathy is remarkably similar to the severe spectrum of disorder observed in human, the canines recapitulate the most important phenotypes observed in humans such as progressive muscle weakness, contractures, non-ambulation, and the muscular signs on biopsy includi...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_9de84294-8404-4bd0-a7c6-89a9a70eb408-2022-09-26T160000.000Z	487	PubMed:26438297
Chen_Rescue Mouse	Rescue Non-human model organism	Chen JC, et al., 2020, PMID: 31481471	Using this method, authors showed that the enzyme gets precisely delivered to acidified lysosomes, where it exists as a stable dimer and results in substrate clearance in the brain tissue of affected mice. Authors suggest that once the uptake capacity of lysosomes was saturated, the remaining extracellular enzyme was l...	Score	2 (2)	Default points are scored.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_0019c7ef-4e2f-4f32-ab42-decfa0b20c29-2023-04-28T160000.000Z	900	PubMed:31481471
V1316M Knock-in Mice	Model Systems Non-human model organism	Adam F, et al., 2016, PMID: 27212476	Homozygous KI-mice replicated human VWD-type 2B with macrothrombocytopenia (platelet counts reduced from 1019x10^3 to 455x10^3/uL, platelet volume increased by 44%), circulating platelet aggregates, reduced high molecular weight multimers, and a severe bleeding tendency with all mice failing to stop bleeding in a tail ...	Score	3 (2)	The V1316M, initially identified in humans, was knocked in to mice, which display a distinct VWD-type 2B phenotype, severe for the homozygous KI-mice and more moderate for the HET-mice. In humans, VWD-type 2B is of dominant inheritance and is usually present in a heterozygous state. In the murine model, although HET-mi...	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_ecfe8bc1-5a4b-4d41-80d1-217af5b5b77f-2020-09-23T160000.000Z	2,332	PubMed:27212476
RNA expression in human cadaver eyes	Expression A	Zhang T, et al., 2021, PMID: 33553197	RNA expression analysis in human cadaver eyes confirmed wide expression of SNRNP200 in multiple eye tissues including cornea, iris, lens, vitreous body, sclera, retina, and optic nerve.	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_41acb15c-18a0-412b-a308-66a7f4e2837a-2022-05-24T160000.000Z	2,061	PubMed:33553197
Murine model	Model Systems Non-human model organism	Gomes J, et al., 2012, PMID: 22240500	ARVC patients carrying heterozygous DSP mutations experienced unexplained syncope, ventricular tachycardia or ventricular fibrillation. Isochronal mapping identified a clearly prolonged reight ventricular depolarization (outflow tract) in these patients. Immunohistochemistry from biopsies from DSP-ARVC patients reveale...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b23da580-269c-4e5d-8f13-91dbe7ea6a57-2019-07-12T160000.000Z	661	PubMed:22240500
Munis Cell Culture Rescue	Rescue Cell culture model	Munis AM, et al., 2021, PMID: 33426150	Following the rescue, immunoblotting showed SFTPB knockout cells with expression of mature SPB homodimer and transepithelial electrical resistance (TEER) levels increased to be comparable with wild type SALI cultures. Treatment with a control vector expressing EGFP failed to generate SPB homodimers and did not correct ...	Score	0.5 (1)	Score reduced as cell culture model evidence from the same paper is scored.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_4bfa265f-3b7a-4091-8e97-b13a7f4f2de7-2024-10-17T190000.000Z	1,966	PubMed:33426150
K78R knock-in mouse model	Model Systems Non-human model organism	Colombo S, et al., 2023, PMID: 37275776	Variant-specific mouse model demonstrates features associated with developmental and motor delay (figure 1) and recapitulates a seizure phenotype that is often reported in individuals with GNB1-related neurodevelopmental disorders (figure 2). The seizure phenotype was demonstrated by EEG (figure 2) and further studied ...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_f83c8548-99d7-489d-8582-ac4ad5abd0ec-2023-08-16T040000.000Z	2,939	PubMed:37275776
MYOC Mutations Activate Stress Pathway	Functional Alteration Non-patient cells	Itakura T, et al., 2015, PMID: 26396484	The wild-type MYOC protein was found entirely in the cell culture medium, while the mutant proteins were retained entirely in the cell according to western blot analysis. The activity of stress-response genes associated with glaucoma, such as IL1A, ACTA2, and FOXO1 were increased in these cells similarly to those found...	Score	0.5 (0.5)	This evidence shows that mutant MYOC accumulating influences the stress pathway, causing cell toxicity and apoptosis. It also upregulates stress genes seen in glaucoma patients. This evidence is enough to earn default points.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_fe5896cf-ec59-431e-bf95-02de61729269-2022-02-17T170000.000Z	1,448	PubMed:26396484
Peden_Rescue	Rescue Cell culture model	Peden AA, et al., 2002, PMID: 11807095	Cells expressing the wild-type Ap3d1 take up less anti–LAMP-1 than non-trandfected cells, indicating less misrouting of LAMP-1 to the plasma membrane in them.	Score	0.5 (1)	The evidence is awarded minimum points as the rescue pertains to a molecular aspect and not the disease phenotype.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_3ec9ffa2-efda-446d-a848-e6d4d5b92fb6-2023-06-07T160000.000Z	2,510	PubMed:11807095
Rescue experiment in Zebrafish model	Rescue Non-human model organism	Ramirez IB, et al., 2012, PMID: 22210625	Phenotype of brain size, apoptosis, and proliferation in OCRL deficient zebrafish embryos can be partially rescued by expression of wild type but not mutant OCRL	Score	1 (2)	Zebrafish cDNA, not human cDNA is used for rescue experiment	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5140c756-fac0-435b-8f59-a5d4a0b0adb3-2020-07-10T160000.000Z	1,582	PubMed:22210625
Redig knockout mouse	Model Systems Non-human model organism	Redig JK, et al., 2014, PMID: 25328912	Knock-out CRELD1 mice presented fewer cells and less extracellular matrices in the atrioventricular endocardial cushions than wild-type mice. Creld1 knockout mouse model combined with increased VEGFA showed abnormal morphogenic response to VEGFA in Creld1-deficient embryonic hearts, indicating that interaction between ...	Score	1 (2)	Genotype does not match human patients	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_1aa67af6-c8df-4151-98ab-049b69fefd08-2023-09-05T160000.000Z	529	PubMed:25328912
In situ hybridization of PRPS1a and b in zebrafish inner ear	Expression A	Pei W, et al., 2016, PMID: 27425195	In situ hybridization of PRPS1a and PRPS1b in zebrafish was found to be relatively enriched in the inner ear, embryonic brain and caudal hematopoiteic tissue.	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_9416f6e2-8de3-48b0-9a1c-9bd11a59315c-2020-02-14T170000.000Z	1,769	PubMed:27425195
Col6A2 KO mouse	Model Systems Non-human model organism	Meehan TF, et al., 2017, PMID: 28650483	Mice displayed decreased grip strength consistent with the muscle weakness observed in patients.	Score	0.25 (2)	Col6A KO mice were not well described, only a decreased grip strength was noted as such full recapitulation of human disease cannot be confirmed. Additionally, the mechanism of disease here (homozygous knockout) does not match the dominant negative mechanism being evaluated in this curation.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_a7a4dad5-f179-44ac-adcb-c5e15c11a1ec-2022-06-27T160000.000Z	488	PubMed:28650483
Byun et al. Rescue in patient cells	Rescue Patient cells	Byun M, et al., 2013, PMID: 23897980	Despite expressing low levels of OX40 on the cell surface, the patient had completely abolished OX40 ligand binding on PHA activated T cells. Lentiviral transfection of OX40-WT rescued this phenotype, restoring OX40 ligand binding in patient T cells. Meanwhile, lentiviral transfection of the patient variant OX40-R65C, ...	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_4759ec3f-6876-41c4-a6eb-fdceedccbc60-2023-06-15T170000.000Z	2,205	PubMed:23897980
Rela+/− mice	Model Systems Non-human model organism	Badran YR, et al., 2017, PMID: 28600438	TNF stimulation of Rela+/− splenocytes resulted in significantly impaired up-regulation of Il6, Tnfaip3, and Traf1; all which depend on NF-κB activation. A low-dose, s.c. TNF injection had no effect on WT mice but resulted in cutaneous ulceration in Rela+/− mice, which was notable for epidermal skin loss and a predomi...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_1e0145f5-c001-420c-9591-c6583862a7ca-2023-09-21T160000.000Z	1,842	PubMed:28600438
C. elegans CMTX6 knock-in model	Model Systems Non-human model organism	Narayanan RK, et al., 2021, PMID: 34387338	The C. elegans models generated in this study recapitulate various molecular phenotypes observed in both the CMTX6 fibroblasts and iPSC-derived motor neurons, and motor phenotypes observed in patients.	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_508a1db7-0cf1-4c28-9203-89a3f4d7438d-2024-03-14T160000.000Z	1,640	PubMed:34387338
Biochemical function 1	Biochemical Function A	Stessman HA, et al., 2017, PMID: 28191889	KMT5B as one of a group of epigenetic modifier genes that are critical for typical neurodevelopment, such as EHMT1 and ARID1B, which are associated with Kleefstra syndrome (OMIM: 610253) and Coffin-Siris syndrome (OMIM: 135900). KMT enzymes (KMT5A, B, anc C) play an epigenetic role by acting as histone methyltransferas...	Score	0.5 (0.5)	Shares a function with other genes associated with neurodevelopmental disorders.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_885d56b0-a2b0-4a3d-9f11-4034298e074e-2022-04-08T072351.945Z	1,177	PubMed:28191889
siRNA mediated CDT1 knockdown in control fibroblasts	Functional Alteration Non-patient cells	Stiff T, et al., 2013, PMID: 23516378	impaired BrDU incorporation, impaired cilia formation, increased centrosome number, and aberrant chondroinduction phenotype. Similar alterations have been observed in ORC1-deficient patient cells, another gene implicated in pathogenesis of MGS	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_dfc9602f-fb88-419a-8955-6d7c00a52158-2023-03-03T170000.000Z	366	PubMed:23516378
Conditional mouse knockdown	Model Systems Non-human model organism	Cabello-Rivera D, et al., 2019, PMID: 31297047	Ndufs2 flox/– alleles and the hGFAP-Cre transgene (hGFAP-NDUFS2 mice) postnatal day (P) 0 hGFAP-NDUFS2 mice were apparently indistinguishable from littermates and their brains were macroscopically similar to controls (Figure 1A), the histological analyses revealed a decrease in cortical thickness (Figure 1B) and subtle...	Score	2 (2)	Reduction MCI, reduction in ATP synthesis, Phenotype: regression and ataxia	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_6df726c1-2897-46f8-aed1-f9939b9acf0c-2021-04-09T143144.546Z	1,499	PubMed:31297047
Overexpression rescue the cell KO phenotype	Rescue Cell culture model	Minaidou A, et al., 2018, PMID: 29845787	growth recovery with formation of early neurites. Patient variant failed to rescue the phenotype	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_82dac4c0-801f-4704-b59d-0a9441423d5a-2023-11-28T170000.000Z	1,230	PubMed:29845787
RC phosphorylation	Biochemical Function B	Muthu P, et al., 2012, PMID: 21696541	Show that MLCK (MYLK2) can phosphorylate RLC (MLC2/MYL2) and modulate myofibrillar ATPase activity. Looking at the WT OE transgenic human ventricular mysoin RLC mouse and tissue.	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_6f0f41e3-7b5b-477c-b45d-598b5f8f3df0-2023-02-08T170000.000Z	2,600	PubMed:21696541
Complex II structure	Biochemical Function A	Fullerton M, et al., 2020, PMID: 33162331	Pathogenic variants in these genes are associated with Leigh syndrome: SDHA- GDR is moderate by ClinGen SOP v6 SDHB- GDR is moderate by ClinGen SOP v8 SDHD - SDHAF1-GDR is limited by ClinGen SOP v7	Score	0 (0.5)	Not scored at this time due to lack of genetic evidence. Can be scored upon availability of genetic evidence.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_909982e0-a53c-4a87-bf28-cdb563c8ae62-2022-03-07T170000.000Z	1,940	PubMed:33162331
Rescue of siRNA treated cells	Rescue Cell culture model	Brooks SP, et al., 2010, PMID: 20332100	Re-expression of the NHS-1A isoform reduced the cell surface area, similar to control/WT cells. Also, the lamellapodia phenotype was ameliorated upon re-expression of NHS-1A.	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_a7f57ca3-efb2-4333-9ae1-732aa429f37a-2017-10-20T040000.000Z	1,539	PubMed:20332100
POMGNT2 knockout in HAP1 cells	Functional Alteration Non-patient cells	Endo Y, et al., 2015, PMID: 27066570	HAP1 POMGNT2 knockout cells exhibited defects in their reactivity to the anti-α-dystroglycan antibody IIH6, which detects the glycosylated form of α-dystroglycan, when observed by fluorescent microscopy. Furthermore, no glycosylated α-dystroglycan was visible in western blot of protein from HAP1 POMGNT2 knockout cells.	Score	1 (0.5)	The score for this functional alteration evidence was upgraded to 1 point from a default of 0.5 points given the ability of the wild type POMGNT2 cDNA to rescue the α-dystroglycan glycosylation defects in HAP1 POMGNT2 knockout cells.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_522f3d3f-8026-439f-9318-2e4df6097a2e-2024-08-14T190000.000Z	2,853	PubMed:27066570
Ubtf E210K expression in mouse fibroblasts	Functional Alteration Non-patient cells	Tremblay MG, et al., 2022, PMID: 35139074	Ubtf E210K/E210K mouse embryonic fibroblasts had >40% lower rate of pre-rRNA synthesis, >40% less RNA polymerase I loading across the rDNA, reduced SL1 (another transcription factor for RNA polymerase I) and UBTF recruitment to the rDNA promoter, and 30% less total cellular RNA. Unexpectedly, the Ubtf E210K mouse fibro...	Score	0.25 (0.5)	These experiments were performed in fibroblasts from embryonic mice homozygous for the E210K variant whereas patients are heterozygous.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_1a5d6060-b955-49a0-9804-265838495310-2023-08-16T190000.000Z	2,296	PubMed:35139074
Restoration of peroxisome morphology	Rescue Patient cells	Costello JL, et al., 2017, PMID: 28108524	Reintroduction of MFF resulted in formation of numerous spherical peroxisomes, restoring the normal phenotype	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_021d15d7-dbf0-4b71-bbb5-48dc4a4b5ee6-2024-06-21T160000.000Z	2,815	PubMed:28108524
Yeast two hybrid analysis: ODA16 and IFT46	Protein Interaction	Ahmed NT, et al., 2008, PMID: 18852297	ODAs are actively transported into cilia via the intraflagellar transport (IFT) system and the transport adaptor ODA16. IFT46 is a core component of the intraflagellar transport machinery and is required for the formation of all cilia. Knockdown of IFT46 causes shortening of the body axis as well as the formation of fe...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_999c6072-d9c6-4339-aea7-8247941748a6-2024-07-11T160000.000Z	575	PubMed:18852297
BCL11A structural and behavioral abnormalities in mice	Model Systems Non-human model organism	Dias C, et al., 2016, PMID: 27453576	Mouse model showed alterations in cognition and brain morphology similar to that described in Dias-Logan syndrome patients. Using a number of different behavioral paradigms, Bcl11a haploinsufficient mice were found to have impaired cognition, abnormal social behavior, and microcephaly, in line with intellectual disabil...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_9630f9a3-3f90-49c6-ae8b-6313c950b1b2-2020-09-13T171807.228Z	220	PubMed:27453576
Panda Mouse Model	Model Systems Non-human model organism	Panda SP, et al., 2013, PMID: 24086598	The aberrant development of the skull upon POR deletion in osteoprogenitor cells in this mouse model not only implicates POR in bone development but it recapitulates, at least partially, the observed craniofacial deformities and bone defects leading to fracture in severe POR-deficient human patients	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_6275d46a-f005-45f8-b3ec-e9722f8dd39e-2022-03-23T193729.312Z	1,733	PubMed:24086598
UROC1 in Histidine Metabolism	Biochemical Function B	Glinton KE, et al., 2019, PMID: 30619714	Defects in this section of histidine metabolism would certainly cause the biochemical abnormality characteristic of this disorder, urocanic aciduria, due to the buildup of the metabolite directly before this step in the pathway.	Score	2 (0.5)	As the function of urocanase in histidine metabolism is very well-characterized, and the biochemical abnormality characteristic of the disorder is a direct result of the loss-of-function in this enzyme, this evidence scores maximum points.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_af2ff293-39ce-46b7-af58-01e3685f4334-2024-04-26T160000.000Z	2,926	PubMed:30619714
Zebrafish null	Model Systems Non-human model organism	Albers CA, et al., 2011, PMID: 21765411	The model system recapitulates human phenotypes of thrombocytopenia and abnormal bleeding, manifested as spontaneous bleeding the the tail of the MO-zebrafish.	Score	1 (2)	The zebrafish recapitulated human phenotypes but was more severe, which may be expected due to the difference between a null-phenotype in zebrafish and a loss of function one in the GPS cases. Also the typical GPS platelet morphology (i.e.absent alpha-granules) was not observed due to the complete abrogation of thrombo...	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_ae8bd4d6-8810-423b-83e0-98667f06426d-2019-06-26T160000.000Z	1,464	PubMed:21765411
STAT3 DNA binding	Functional Alteration Non-patient cells	Asano T, et al., 2021, PMID: 34137790	Transfection of variants into HEK293 cells resulted in the reduction of STAT3 DNA binding for the majority of variants. For those variants without decreased DNA binding, alternative splicing was investigated, and it was found that alternative transcripts or translation reinitiating were being generated that resulted in...	Score	1 (0.5)	This is an extensive work that demonstrates the vast majority of STAT3 LOF variants are dominant negative and not loss of heterozygosity. I have upgraded the score due to the vast number of variants tested, as well as the quality of the data generated.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_beb3aa5b-240e-45d7-969a-9de3e5564457-2021-12-24T160548.234Z	2,104	PubMed:34137790
Mouse model	Model Systems Non-human model organism	Alharatani R, et al., 2020, PMID: 32196547	The cleft palate and brain structural anomalies seen in the mice reflect anomalies seen in affected humans.	Score	1 (2)	The heterozygous mutants had no cleft lip/palate, or facial/arm/leg anomalies, so the score is downgraded.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5000144a-71c1-4ae7-95a9-17ad67a388c5-2024-03-21T160000.000Z	552	PubMed:32196547
Neulen 2009 FunctAlt1	Functional Alteration Non-patient cells	Neulen A, et al., 2009, PMID: 19506933	Effect of L29Q on isometric force and unloaded shortening velocity in triton-skinned myocardium. Results showed no statistical significance.	Score	0 (0.5)	Triton-skinned myocardium preparations have no functional cell membranes or sarcoplasmic reticulum, but myofilamint lattice is intact.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5d832673-8acb-4a02-ae34-35e0d9981b70-2023-09-13T160000.000Z	2,208	PubMed:19506933
Omran et al. 2008 Chlamydomonas	Model Systems Non-human model organism	Omran H, et al., 2008, PMID: 19052621	One of the recurring phenotypes of PCD in human patients is ODA and IDA defects. This experiment with Chlamydomonas demonstrates loss of motility (paralyzed flagella) as well as recurrence of the partial ODA and IDA loss.	Score	1 (2)	Downscored due to the model being unable to display the respiratory phenotypes like humans	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_39e5de96-3f16-4dde-a7bc-b3e27364b7f8-2024-02-08T170000.000Z	615	PubMed:19052621
TECRLc.331+1G>A characterisation	Functional Alteration Patient cells	Devalla HD, et al., 2016, PMID: 27861123	Analysis of intracellular calcium ([Ca2+]i) dynamics revealed smaller [Ca2+]i transient amplitudes as well as elevated diastolic [Ca2+]i in TECRL-homozygous-hiPSC-CMs with the TECRLc.331+1G>A mutation compared with Control-hiPSC-CMs. The [Ca2+]i transient also rose markedly slower and contained lower sarcoplasmic retic...	Score	2 (1)	In-depth characterisation of variant effect with numerous assays and multiple effects demonstrated.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_6889dc44-eef0-4a4d-8fdb-aef2dc570f29-2021-01-20T170000.000Z	2,161	PubMed:27861123
Li Protein Interaction	Protein Interaction	Li D, et al., 2013, PMID: 23325789	Many binding partners of DIAPH1 were identified, including ACTB and ACTG1, several tubulins, and OSBPL2, a moderate hearing loss gene	Score	0.5 (0.5)	No connection made to hearing loss, but supports role in regulation of microfilament/microtubule function, which are important in hair cells. Downgraded to 0.25, however scoring for this model is combined with Carreira 2003 study to equal 0.5 points.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_43c017fd-ce70-4fbe-ad30-90f216adaa7d-2018-01-05T170000.000Z	598	PubMed:23325789
Misato Drosophila	Model Systems Non-human model organism	Min S, et al., 2017, PMID: 29255146	In this study, we have shown that depletion of mst in the whole muscle tissues specifically impaired intestinalfunctions while skeletal muscles remained unaffected. Having shown that depletion of mst in the Drosophila visceral muscle elicits a series of intestinal phenotypes, we wondered whether genetic restoration of ...	Score	0.5 (2)	Scored 0.5 points because of imperfect phenotype overlap - (visceral myopathy v. skeletal myopathy, some evidence for visceral myopathy as well)	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_10089a58-c9b4-497a-afb0-d249220eb2aa-2023-05-18T160000.000Z	1,341	PubMed:29255146
mitophagy defects in dopaminergic parkin mutant patient neur	Functional Alteration Patient cells	Schwartzentruber A, et al., 2020, PMID: 32968089	There was significant cell death occurring throughout differentiation specifically in the PRKN mutant patient derived DA neurons; the percentage of cells surviving until the end of the differentiation was significantly reduced (mean ± SD, controls 83.62 ± 4.8; parkin mutants 52.72 ± 11.98) We observe the same mitochond...	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_6b39c4a0-f6bd-4afc-b2a7-f234eab5a667-2023-01-18T190000.000Z	1,759	PubMed:32968089
MEF2C Neocortical and hippocampal KO mice	Model Systems Non-human model organism	Harrington AJ, et al., 2016, PMID: 27779093	The homozygous MEF2C floxed, Emx1-Cre mice (Mef2c cKO) were tested for a number of behavioral paradigms associated with learning and memory, and social interaction. Ultrasonic vocalization (USVs) were recorded in Mef2c cKO mice versus control littermates. The Mef2c cKO adult male mice prodiced 70% fewer USV calls in th...	Score	3 (2)	This mouse model follows the molecular mechanism described in the humans with MEF2C variation (loss of function) and outlines several behavioral deficits that are consistent with learning and memory and social deficits. Furthermore, RNA-seq performed on specific brain regions in the knockout mice show reduction in the ...	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_34354e8f-4343-4fba-82ba-e49579e504bb-2019-02-06T170000.000Z	1,277	PubMed:27779093
Xenopus Model	Model Systems Non-human model organism	Alharatani R, et al., 2020, PMID: 32196547	The fact that the mutants had small craniofacial cartilages and reduced survival falls in line with the craniofacial phenotype seen in humans. The abnormal heart looping seen in the mice falls in line with the ventricular and atrial septal defects seen in a few affected human probands.	Score	1 (2)	Downgrading as the phenotype is not super specific to the craniofacial features seen in humans.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5000144a-71c1-4ae7-95a9-17ad67a388c5-2024-03-21T160000.000Z	552	PubMed:32196547
HEK transfection	Functional Alteration Non-patient cells	Gao J, et al., 2015, PMID: 26196677	WT MCM2-transfected cells had significantly fewer apoptotic cells after 48h than mutant MCM2-transfected culture, and both were significantly higher than the culture that lacked exogenous MCM2. These results support that MCM2 has pro-apoptotic activity. The same results were seen with Western blot of whole cell lysates...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_29172723-c896-4cbf-a20b-9921fc72547f-2020-04-21T190000.000Z	1,263	PubMed:26196677
Function	Biochemical Function B	Blackburn PR, et al., 2017, PMID: 28919799	Disruption of any subunit of the BCKAD complex leads to an increase and BCAAs, causing toxicity of tissues.	Score	1 (0.5)	Well-known disease mechanism. Review: MSUD is caused by decreased function of the BCKAD enzyme complex, which is composed of E1, E2 (encoded by DBT) and E3 subunits. The BCKAD complex is involved in the second step of catabolism of branched-chain amino acids (BCAAs), which are essential for life.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_cfd1ebde-e447-4877-977e-f5b9fe434adc-2018-10-30T160000.000Z	576	PubMed:28919799
KO Mouse	Model Systems Non-human model organism	Reinholt BM, et al., 2013, PMID: 23626854	Both the affected mice and humans biopsy revealed myopathic changes and fiber size variability.	Score	1 (2)	Showed that Stac3 is essential for development of functional skeletal muscle and viable mice. This knockout model had a phenotype more severe than that observed in humans, causing neonatal lethality.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_940572b9-6a5a-4de1-8ee1-6394f589515f-2020-04-25T160000.000Z	2,672	PubMed:23626854
Mdm4 TM/TM MEFs	Model Systems Cell culture model	Toufektchan E, et al., 2020, PMID: 32300648	MDM4 is a negative regulator of p53. This culture model demonstrated that loss of function of MDM4 results in an increased activity of p53 and short telomeres, features observed in humans with germ line mutations.	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5c4e0701-22d0-4e73-bf76-a23e9472fe3d-2024-12-10T170000.000Z	2,969	PubMed:32300648
Le Coz_in vitro	Model Systems Cell culture model	Le Coz C, et al., 2021, PMID: 33951726	The authors demonstrate that biallelic PU.1 ETS expression is important for human B and myeloid cell development in vitro, similar to that seen in humans. Following the gene alteration to model PU.MA patient haematopoiesis (as described above), surviving myeloid (CD33+) or B cell precursors (CD19intIgM−, CD19hiIgM−, or...	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_76a93861-b7d3-4d08-8882-6a7a1456b51a-2024-12-12T170000.000Z	2,966	PubMed:33951726
Mutations in Hydin impair ciliary motility in mice	Model Systems Non-human model organism	Lechtreck KF, et al., 2008, PMID: 18250199	The paper provides evidence on lack of central pair projection and abnormal ciliary bending in HYDIN mutant mice. Both defects are observed in humans and are responsible for inefficient mucociliary clearance observed in PCD patients. Moreover, hy3/hy3 mice, situs abnormalities, as judged by the analysis of lung lobatio...	Score	3 (2)	The paper continued previous work by Davy and Robinson, 2003 where Two mutant alleles of Hydin (hy3 and OVE459) have been characterized with no transcripts have been detected. Both structural and functional defects in the brain and tracheal cells of HYDIN mutant mice. Phenotypes and (non phenotype) matches their human ...	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_6c491ab7-496f-43b9-9bca-500901cb686d-2022-02-22T183411.247Z	1,031	PubMed:18250199
Purification of human cohesin complexes.	Protein Interaction	Sumara I, et al., 2000, PMID: 11076961	human cohesin complexes	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_c281f5fd-d868-4425-a7b4-8e39e3b2090e-2019-06-19T160000.000Z	2,666	PubMed:11076961
Complex II structure	Biochemical Function A	Fullerton M, et al., 2020, PMID: 33162331	All the above genes are structural components of complex II.	Score	1 (0.5)	1 point as per LSS GCEP rubric	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_9010c629-a86c-4f55-a45b-212b7aabdb6f-2022-04-04T160000.000Z	1,941	PubMed:33162331
FA Nonpatient Cells	Functional Alteration Non-patient cells	Dhindsa RS, et al., 2015, PMID: 27066543	Expression of mutant proteins decrease endocytosis activity in dominant negative manner. The G359A variant showed disrupted higher-order DNM1 oligomerization. EM of mutation DNM1-transfected HeLa cells and DNM1 mutate mice showed vesicle defects indicating vesicle scission activity	Review	0.5 (0.5)	This is variant-level functional evidence. I have removed it from the experimental evidence total and instead applied it as supporting evidence for the individual with the G359A variant. Expression of mutant proteins decrease endocytosis activity in dominant negative manner.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_31f598a3-7efd-4e43-83f3-587e98924260-2024-02-06T080000.000Z	2,748	PubMed:27066543
Deaf14 mouse	Model Systems Non-human model organism	Carpinelli MR, et al., 2014, PMID: 24682784	In humans, Canavan disease is a leukodystrophy characterized by spongiform encephalopathy of the brain, progressive intellectual impairment, motor deficit, and death in childhood. Additional clinical symptoms include hearing and visual impairment and seizures. Deaf14 mice were generated by ethyl-nitrosonurea screen and...	Score	3 (2)	The score is increased because the mice are homozygous for a loss of function variant, as is observed in human cases, and several key features of Canavan disease are present. The biochemical features, such as increased NAA, were not reported.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_66306eff-659f-4508-a41b-1820e47e0e1d-2020-10-08T161701.633Z	170	PubMed:24682784
Mouse in situ hybridization	Expression A	Mommersteeg MT, et al., 2015, PMID: 25691540	Mouse ISH at E16.5	Score	0 (0.5)	Already scored for this expression in another study	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_a0d0c93c-abf7-4bf2-8b0f-e47cfce87656-2024-09-03T160000.000Z	1,876	PubMed:25691540
AP4E1 Knockout mouse	Model Systems Non-human model organism	De Pace R, et al., 2018, PMID: 29698489	Impaired motor coordination and weak grip strength seen in AP4E1 KO mice is consistent with impaired motor development, hypotonia and spastic paraplegia in humans Thin corpus callosum found in AP4E1 KO mice is similar to thinning of corpus callosum in human patients. Mislocalization of ATG9A (AP4 cargo) in AP4E1 KO mic...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_be93d2e7-f302-41a7-9675-032510e46ad2-2020-12-16T170000.000Z	2,698	PubMed:29698489
Lentiviral Vector Rescue	Rescue Patient cells	Izawa K, et al., 2017, PMID: 28011863	The lentivirus induced surface expression of CD70 to levels comparable with those seen on LCLs from control donors	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_69aa819c-1f25-42fe-8469-4641fc088a57-2025-02-05T170000.000Z	2,989	PubMed:28011863
Zhang patient cells	Functional Alteration Patient cells	Zhang S, et al., 2023, PMID: 36579833	Quantitative analysis of the number, total area, average length and total signal intensity per visual field (0.143 mm2) of AChR clusters in C2C12 cells expressing WT-DOK7 or p.G64R-DOK7/p.G64R-DOK7 markedly reduced AChR clustering.	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b40a6c0a-1152-4d29-8ba3-1136600085b9-2025-02-24T170000.000Z	3,017	PubMed:36579833
Wang_Functional Alteration	Functional Alteration Patient cells	Wang L, et al., 2020, PMID: 32788587	By day in vitro 52, affected organoids were noticeably smaller than unaffected organoids. By day in vitro 90, the majority of unaffected COs were >5 mm, while none of the affected COs were >5 mm, and most were <1 mm diameter.	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_c46ba676-3297-4e2c-a88f-bc479c32de60-2024-03-06T170000.000Z	1,459	PubMed:32788587
Serpas_2019_Plasma DNA Fragmentation by DNASE1 +DNASE1L3	Biochemical Function A	, , PMID: 30593563	DNASE1L3 is also an endonuclease capable of cleaving both single- and double-stranded DNA that has been strongly associated with SLE in a loss-of-function autosomal recessive pattern. This experiment shows the effect of deletions in DNASE1L3 only, DNASE1 only, DNASE1 + DNASE1L3, and WT mice on the degree of plasma DNA ...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b71d9246-5a7e-4e81-8fc6-925181d124cd-2024-06-14T190000.000Z	635	PubMed:30593563
ER localization	Biochemical Function B	Gerondopoulos A, et al., 2014, PMID: 24891604	Control and patient fibroblasts were fixed and stained with antibodies to CLIMP-63 and reticulon 4 (Rtn4). In comparison to control fibroblasts, CLIMP-63 spread away from the perinuclear region into the cell periphery and clearly defined Rtn4-positive tubules were lost in both the Rab18 L24Q and Rab3GAP1 (c.649-2A>G) p...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_a322fa3e-2985-4f60-9b4b-87f333cf9431-2023-11-28T200000.000Z	1,804	PubMed:24891604
Subcellular localization and pH homeostasis	Functional Alteration Non-patient cells	Prasad H, et al., 2017, PMID: 28815171	No subcellular localization or expression change was observed. No loss-of-function was observed with respect to endosomal pH homeostasis and transferrin endocytosis.	Score	0 (0.5)	No functional alteration observed for these variants.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_463ee005-1264-45da-bd85-3776a6637c68-2020-10-08T160000.000Z	2,030	PubMed:28815171
Mouse single cell transcriptomics	Expression A	de Soysa TY, et al., 2019, PMID: 31341279	Detection via single cell RNA sequencing	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7a70bdb1-a3fc-45c5-aabb-4d2829fa6f29-2023-04-04T160000.000Z	961	PubMed:31341279
Electron cryomicroscopy structure of complex I	Biochemical Function A	Zhu J, et al., 2016, PMID: 27509854	Mammalian complex I contains 45 subunits, comprising 14 core subunits that house the catalytic machinery and are conserved from bacteria to humans, and a mammalian-specific cohort of 31 supernumerary subunits. Zhu et al. present a structural model of complex I.	Score	2 (0.5)	Scored 2 pts per scoring rubric (> 10 proteins associated with PMD)	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_fbdf3ba5-37d8-447d-888b-2762701bab49-2022-03-07T050000.000Z	1,483	PubMed:27509854
Naturally occurring Nme5-related canine PCD model	Model Systems Non-human model organism	Anderegg L, et al., 2019, PMID: 31479451	Alaskan Malamutes harboring the homozygous variant in NME5 exhibit lack of situs inversus, severe bronchial lung pattern with bronchiectasis (Figure 1), hyperemia of the tracheal mucosa with high mucopurulent secretion along the upper and lower airways and nasal cavitiy (Figure 1). Bronchoalveolar bacterial cultures we...	Score	2 (2)	The degree of phenotypic match between the affected animals and the NME5-deficient human patients have led to a recommendation of default scoring. The variant was naturally occurring in Alaskan Malamutes rather than a targeted mutation, and has not been observed in an affected human patient.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_00efe110-5916-4da0-92ac-cee8c8b18140-2024-02-08T170000.000Z	1,542	PubMed:31479451
Expression of CCDC65 during ciliogenesis	Expression A	Horani A, et al., 2013, PMID: 23991085	null	Score	1 (0.5)	Two separate experiments validated the expression of CCDC65 in PCD relevant tissues and during ciliogenesis	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_662ab516-ba5f-46aa-97b2-ef4c8f3201a5-2024-08-08T160000.000Z	327	PubMed:23991085
Yan_Mouse Model	Model Systems Non-human model organism	Yan L, et al., 2023, PMID: 37228654	The Wdr60 PB/PB embryos had much less cilia than WT embryos. The human phenotype is a skeletal ciliopathy, which is caused by defects in the function of cilia.	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_ad85ec94-69a9-4e67-a366-5ec2d574f1e4-2024-09-04T160000.000Z	669	PubMed:37228654
DICER KO MSC rescue	Rescue Cell culture model	JnBaptiste CK, et al., 2017, PMID: 28446596	miRNA expression was rescued and the endogenous targets of the miRNA, mRNA, expression pattern correlated with previous reported changes. doxorubicin-induced sensitivity (culminating in cell death) was also returned to wildtype levels. Some specific miRNA target mRNAs remained activated, authors explain as a 'stable st...	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_aeabfc3b-63a9-40f2-9c71-41b079fee4e2-2023-07-05T170000.000Z	600	PubMed:28446596
Mitochondrial fusion assay	Functional Alteration Non-patient cells	Chen H, et al., 2003, PMID: 12527753	Two ovoid mitochondria contact each other but do not fuse until much later. Unfused mitochondria	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_a04350b3-5fe9-438a-9e90-db0055ed15e7-2022-10-10T160000.000Z	1,287	PubMed:12527753
DDOST variants affect LOX N-glycosylation	Functional Alteration Non-patient cells	Kas SM, et al., 2023, PMID: 37848450	LOX N-glycosylation was also restored by DDOST p.G200D, p.S206P and p.R379Q, but not by p.L364Ffs11 or p.I405Tfs7.	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_e0605b51-70c5-42ee-81b5-d45bb0b1fdab-2023-11-15T170000.000Z	2,987	PubMed:37848450
Depletion of p150 in mice neurons	Model Systems Non-human model organism	Yu J, et al., 2018, PMID: 29490687	The loss of SMN with a late onset, loss of motor control, muscle atrophy, and gliosis are all features commonly observed in patients with ALS.	Score	1 (2)	No differences of cerebral spinal motor neurons. Lack of clinical similarity to ALS (eg. lifespan)	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5cd19f2c-2499-417f-94c8-2bd4bedf34ef-2023-08-04T160000.000Z	583	PubMed:29490687
rhg mouse	Model Systems Non-human model organism	Bisaillon JJ, et al., 2014, PMID: 25264521	A missense variant in Oat, p.Gly353Ala, was found to be the cause of the “retarded hair growth” (rhg) phenotype in mice. Homozygous rhg mice appear normal at birth but they are smaller than their heterozygous littermates by 10 days of age, and have delayed development of a hairy coat that is most obvious at 7–10 days o...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_edbab666-9ae6-46db-b818-809a4bf8333e-2019-07-10T160000.000Z	2,617	PubMed:25264521
Heterozygous conditonal deletion allele for Dynch1h1	Model Systems Non-human model organism	Di Pizio A, et al., 2023, PMID: 36218033	abnormal hind limb posture when suspended by the tail is indicative of motor phenotypes in mice	Score	1 (2)	Downgraded because the disease mechanism in patients is GoF probably and this is a LoF model (discussed at the CMT GCEP meeting)	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_c1e12eb9-aea0-4597-8893-48df533f6ad9-2023-07-12T160000.000Z	668	PubMed:36218033
Global and tissue specific (multiciliated) CEP164 KO mouse	Model Systems Non-human model organism	Siller SS, et al., 2017, PMID: 29244804	At E9.5 and E10.5, CEP164-KO embryos exhibited holoprosencephaly, cardiac looping defects, an edematous pericardial sac, and a truncated posterior trunk. These phenotypes are similar to those reported for mouse mutants for KIF3A and KIF3B, which are major components of the kinesin-II ciliary anterograde motor, providin...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_961b81f6-7ad1-49e2-b675-c035b4d8d35d-2021-10-27T160000.000Z	3,062	PubMed:29244804
Ektacytometry of patient RBCs	Functional Alteration Patient cells	Yamaguchi Y, et al., 2021, PMID: 34737711	Ektacytometry determined that patient red blood cells had increased H2O volume, reduced K+, increased Na+ consistent with increased channel activity.	Score	0.5 (1)	Reduced score as red blood cell phenotype consistent with DHS has also been described rarely for patients with homozygous loss of function PIEZO1 variants.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_6a86cb1d-4eed-4c10-971f-4a9578cb12b1-2023-07-02T040000.000Z	1,674	PubMed:34737711
Rnaseh2c-/- mice	Model Systems Non-human model organism	Hiller B, et al., 2012, PMID: 22802351	Although mouse phenotype was limited for knock-out model due to early embryonic lethality, cells obtained from knock-out mouse embryos demonstrated increased genomic ribonucleotide load consistent with underlying disease mechanism.	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_9f65b554-f11e-41ff-8a6f-dcb5d8484122-2024-08-26T160000.000Z	1,871	PubMed:22802351
BRWD1 mutated mice have hypogammaglobulinemia	Model Systems Non-human model organism	Mandal M, et al., 2015, PMID: 26301565	BRWD1 mutated mice show decreased levels of circulating antibodies like observed in human patients.	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_a44471f3-0951-4456-955d-916b691e59f5-2022-12-08T170000.000Z	255	PubMed:26301565
MTX2 and MTX1 deficiency hampers TNF-α-induced apoptosis	Functional Alteration Patient cells	Elouej S, et al., 2020, PMID: 32917887	The number of dead cells upon apoptosis was significantly reduced in patients compared to control fibroblasts, confirmed by the reduction of Caspase 3 cleavage in MTX2-mutant fibroblasts. Observed Increased macro-autophagy in MTX2 deficient patient fibroblast cells. The mitochondrial dysfunction and hampered apoptosis ...	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_95b2738d-c934-401b-8665-dd6a19ec6a05-2024-06-05T160000.000Z	1,410	PubMed:32917887
Gorelik_Lysosomal multienzyme complex	Biochemical Function A	Gorelik A, et al., 2021, PMID: 33980489	GLB1, CTSA and NEU1 form the lysosomal multienzyme complex together.	Score	0.5 (0.5)	GLB1 protein forms the lysosomal multienzyme complex with the products of two other genes, CTSA and NEU1. Increased points are awarded for the same function as two other genes causing lysosomal disorders.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_9e170fda-e08a-4fd3-a3e5-f08c5c0d55b8-2023-04-28T160000.000Z	901	PubMed:33980489
Zebrafish model	Model Systems Non-human model organism	Halbig KM, et al., 2012, PMID: 22268977	The Zebrafish demonstrates heart defects, ear abnormalities, and other bodily malformations that are also seen in humans.	Score	1.5 (2)	Downscored 0.5 points due to lack of laboratory phenotype reported within this model system.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_d2961595-2f51-45d6-af4d-988ec5a7628a-2024-03-05T170000.000Z	2,379	PubMed:22268977
Review: LeighMap	Biochemical Function A	Rahman J, et al., 2017, PMID: 27977873	Rahman et al. reviews all genes associated with Leigh syndrome in Leigh Map 2017 (PMID: 27977873). These genes included at least thirteen nuclear genes directly involved in mitochondrial translation as well as five additional mt-tRNA genes.	Score	2 (0.5)	per rubric: More than 10 gene with a related function	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_42f2fc91-c26d-416c-8d93-448e4a52983b-2021-04-14T040000.000Z	1,394	PubMed:27977873
Impaired generation of memory B cells	Functional Alteration Patient cells	Cagdas D, et al., 2021, PMID: 33929673	Within the contracted memory B cell population in IL-21R-deficient patients, proportions of IgG+ or IgA+ switched cells were significantly decreased	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_4dbeac16-997c-43c0-9fb6-eaa98d0816f9-2022-12-31T120000.000Z	1,062	PubMed:33929673
Bach2 is required for efficient formation of Treg cells	Biochemical Function B	Roychoudhuri R, et al., 2013, PMID: 23728300	Impaired regulatory T cell function are evident in BACH2 mutant patients compared with healthy controls and also with patients with classical IBD	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_2473560a-6e5c-4342-a6e2-c89e37f4cc71-2023-02-21T180000.000Z	206	PubMed:23728300
Abkevich Expression	Expression B	Abkevich V, et al., 2012, PMID: 23047548	RAD51C promoter methylation was observed consistently in cohorts and the high homologous recombination deficiency (HRD) score showed a significant association with RAD51C deficiency in two data sets and was consistent with scores for BRCA1/2 defects also found in the data sets. Ovarian tumors with LOH show increased ho...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_31cb27be-dd32-4bb7-86bd-43c4b1eabaf5-2024-08-29T170000.000Z	1,814	PubMed:23047548
Wang 2016 knock-in mouse model	Model Systems Non-human model organism	Wang F, et al., 2016, PMID: 27469509	Developed a heterozygous knock-in transgenic mouse strain in which the R140Q (patient variant) was introduced into the native Idh2 locus. Knock-in mice showed higher pre- and peri-natal mortality, runting, facial dysmorphism and abnormal head shape, cardiomyopathy, cardiomyocyte hypertrophy, vacuoles in brain tissue, h...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_91787b5b-8185-48e6-a437-9162c039b454-2023-01-30T170000.000Z	1,038	PubMed:27469509
Neurotransmitter alterations in Aldh5a1-/- mouse embryos	Model Systems Non-human model organism	Jansen EE, et al., 2008, PMID: 19040727	Succinic semialdehyde dehydrogenase deficiency is a disorder of the GABA degradation pathway where consecutive elevation of gamma-hydroxybutyric acid (GHB) and GABA occur. GABA and DHHA (4,5-dihydroxyhexanoic acid) were found to be significantly elevated at all gestational ages in Aldh5a1-/- mice,	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_c3e57466-df2f-4045-b374-010dbd334bfc-2021-04-27T160000.000Z	90	PubMed:19040727
BLOC-2 complex cargo delivery	Biochemical Function B	Dennis MK, et al., 2015, PMID: 26008744	Albinism in HPS patients reflects defects in the biogenesis of melanosomes in melanocytes of the skin, hair, and choroid of the eye and in pigment epithelial cells of the retina, iris, and ciliary body of the eye. While not addressed here, a similar cargo delivery mechanism may be involved in the bleeding and bruising ...	Score	0.5 (0.5)	Live-cell imaging analyses show that BLOC-2 is required for melanosome-destined tubular carriers to make stable contacts with maturing melanosomes. Consistently, BLOC-2 influences the melanosomal delivery of BLOC-1-dependent cargoes, including TYRP1, OCA2, ATP7A, and a cohort of TYR, from early endosomes in mouse melan...	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_a761e746-824f-496c-8d9f-4f8cd50423c3-2020-10-28T160000.000Z	1,016	PubMed:26008744
Ye knockout mouse	Model Systems Non-human model organism	Ye L, et al., 2015, PMID: 25811986	Global Snx10-deficiency in mice results in a combined phenotype of osteopetrosis (due to osteoclast defect) and rickets (due to high stomach pH and low calcium availability, resulting in impaired bone mineralization). Snx10 knockdown (KD) mice exhibited severe growth retardation with failed tooth eruption compared to W...	Score	2 (2)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_4c6f3ffa-405b-4b64-b29d-b4dc157ef586-2024-06-24T160000.000Z	2,063	PubMed:25811986
LRRC56 is part of mouse LRO transcriptome	Expression A	Bellchambers HM, et al., 2023, PMID: 37393374	Single cell RNA sequencing (scRNA-seq) was done to generate a transcriptomic profile list of LRO genes from precisely staged 0–1 somite mouse embryos, when the LRO fluid flow is first detected. LRRC56 was one of 196 transcripts described as the LRO transcriptome. LRO cells have motile cilia and are involved in determ...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_ceef14a8-34d2-41ac-8c03-47c5eaff8986-2024-11-19T200000.000Z	1,227	PubMed:37393374
MMADHC crystal structure	Protein Interaction	Froese DS, et al., 2015, PMID: 26483544	A series of human MMADHC and MMACHC truncation proteins was expressed and interactions between them was assessed using blue native-PAGE and size-exclusion chromatography. The MMADHC region C-terminal to amino acid 154 and the MMACHC region without the C terminus was found to be sufficient for direct protein-protein int...	Score	1 (0.5)	The score is increased due to the level of evidence available including multiple experimental approaches taken to analyze the interaction between MMADHC and MMACHC.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_40ec59af-a143-4424-9218-7fd75deb6a61-2021-05-12T182739.747Z	1,307	PubMed:26483544
Dnah5 siRNA knockout in mouse tracheal epithelial cells	Model Systems Cell culture model	Zahid M, et al., 2020, PMID: 32823934	High-speed video microscopy of cilia beating in human DNAH5 mutants shows a range of effects on cilia motility depending on the particular variants. Phenotypes can range from completely immotile respiratory cilia to altered motility with stiff movements and low amplitudes (Raidt et al PMID:25186273). There was no sig...	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_4390dba1-012d-4e08-a841-ffc08ebdc737-2022-01-07T190607.723Z	624	PubMed:32823934
Mutant expression in endocrinepancreatic tumor of patient	Expression B	Occhi G, et al., 2013, PMID: 23555276	Endocrine pancreatic tumor of the patient having the c.-456_-453delCCTT mutation. Tumor cells show low expression of p27KIP1 in the nucleus but also expression in the cytoplasm. (Fig. 4).	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_b07f8882-dd5e-4831-9926-f8b4c2a8c265-2018-12-21T154854.477Z	364	PubMed:23555276
Immunostaining analysis	Expression A	Porpora M, et al., 2018, PMID: 29581457	Immunostaining analysis confirmed significant fraction of NEK10 is localized at cilia. Serum deprived HEK293 cells were immunostained and acetylated tubulin and analyzed by confocal microscope.	Score	0.1 (0.5)	Recognize as independent assay but showing same datapoint as Chivukula 2020 paper.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_72a2f8fa-ee83-48cc-93fa-22a8990c8d13-2023-07-13T160000.000Z	2,827	PubMed:29581457
Neuron KO of MICU1 in Mice	Model Systems Non-human model organism	Singh R, et al., 2022, PMID: 35302860	Mice should abnormal calcium flux and diminished function on rotarod test and grip test	Score	1 (2)	Score 0.5 for calcium flux abnormalities, Score 0.5 for phenotype	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_4c9276ee-39e6-408f-9ae0-a4c3000f3089-2023-11-20T050000.000Z	1,293	PubMed:35302860
Wnt5a in canonical and non-canonical signaling	Biochemical Function A	Mikels AJ, et al., 2006, PMID: 16602827	The impact of Wnt5a ligand on Wnt signaling was studied in mouse cells and HEK293 cells. STF-luciferase assay was used as a readout of beta-catenin activity. Wnt3a expression activaed the canonical pathway. However, over-expression of Wnt5a inhibited canonical Wnt signaling by Wnt3a in mouse cells (Fig 1). Frizzled 4 r...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_0fb2940f-f0e0-442c-beb8-72fc959d5a43-2024-04-25T160000.000Z	2,932	PubMed:16602827
Mutant CHCHD10 on TDP43 apoptosis and synaptic damange	Protein Interaction	Woo JA, et al., 2017, PMID: 28585542	Wild-type CHCHD10 ameliorates and FTD/ALS CHCHD10 mutations potentiate TDP-43-induced apoptosis and synaptic impairment	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_d154f67a-25ce-40d3-9de3-1f001753843a-2022-09-13T160000.000Z	398	PubMed:28585542
Mitochondrial translation defects	Biochemical Function A	D'Souza AR, et al., 2018, PMID: 30030363	Mitochondrial tRNA	Score	2 (0.5)	Mitochondrial translation defects are a known cause of primary mitochondrial disease.	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_99e85f3e-3c1f-4265-8b70-0870e95d4c30-2023-04-17T160000.000Z	1,393	PubMed:30030363
DSB repair measurements	Functional Alteration Patient cells	Keupp K, et al., 2019, PMID: 31347298	two fold decrease in HR was scored for the LCLs from the mother carrying the BRCA1 p.Arg1699Gln mutation and sixfold for the LCLs from the index patient carrying both mutations; in addition, both LCLs showed four‐ to fivefold elevated microhomology‐mediated end joining compared with three wild‐type LCLs	Score	1 (1)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_aa39798d-9b6e-430d-8bc1-2a01f81f1f72-2020-05-14T003137.538Z	2,525	PubMed:31347298
Alx expression in the developing head of mouse, chick, and f	Expression A	McGonnell IM, et al., 2011, PMID: 21740507	Probands with mutant ALX3 alleles showcase defects in the are expressed in the mesenchyme of the facial prominences, particularly around the nasal region and at the distal tip of the mandible. Regular expression of ALX3 has been confirmed by multiple mouse models: Ten Berge et al. (1998) PMID:PMID: 9676189 and Beverda...	Score	0.5 (0.5)	null	https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_1b460912-d5fd-4b7b-99da-ccd477fd8139-2022-10-13T160000.000Z	108	PubMed:21740507

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YAML Metadata Warning:empty or missing yaml metadata in repo card

Check out the documentation for more information.

CGBench Dataset

This repository contains the CGBench dataset - a comprehensive benchmarking framework for evaluating scientific reasoning in language models using ClinGen (clinicalgenome.org) data. The dataset enables evaluation of language models' ability to extract, interpret, and explain fine-grained results from scientific publications in clinical genetics.

Dataset Overview

CGBench formulates three separate tasks:

GCI Evidence Extraction - Gene-disease association evidence extraction
VCI Evidence Scoring - Variant pathogenicity evidence scoring
VCI Evidence Sufficiency - Evidence sufficiency determination

Directory Structure

GCI/ - Gene Curation Interface Data

Contains data related to gene-disease association evidence extraction tasks.

Core Files

Clingen-Gene-Disease-Summary-2025-03-31.csv

Summary of all ClinGen gene-disease validity classifications
Columns:
- GENE SYMBOL: HGNC gene symbol
- GENE ID (HGNC): HGNC gene identifier
- DISEASE LABEL: Human-readable disease name
- DISEASE ID (MONDO): MONDO ontology disease identifier
- MOI: Mode of inheritance (AD=Autosomal Dominant, AR=Autosomal Recessive, XL=X-linked)
- SOP: Standard Operating Procedure version used for curation
- CLASSIFICATION: Gene-disease association strength (Definitive, Strong, Moderate, Limited)
- ONLINE REPORT: URL to full ClinGen report
- CLASSIFICATION DATE: Date of classification
- GCEP: Gene Curation Expert Panel responsible for classification

SOP/ - Standard Operating Procedures

experimental_evidence/ Contains JSON files defining evidence categories and scoring criteria:

SOP5.json through SOP11.json: Different versions of standard operating procedures
Each file contains structured evidence categories with titles and descriptions for:
- Biochemical Function (A & B)
- Protein Interaction
- Expression (A & B)
- Functional Alteration
- Model Systems
- Rescue experiments

evidence_tables/

experimental_evidence/evidence_cleaned_fulltext.csv

Complete dataset of experimental evidence with full-text paper content
Columns:
- Label: Evidence description/title
- Experimental Category: Type of evidence (e.g., "Model Systems Non-human model organism")
- Reference: Citation with PMID
- Explanation: Detailed explanation of the evidence
- Score Status: Whether evidence was scored
- Points (default points): Numerical score assigned
- Reason for Changed Score: Explanation if score was modified
- url: Link to ClinGen assertion
- primary_index: Internal identifier
- pmid: PubMed identifier

Train/Test Splits:

train.csv, test.csv: Standard splits for model training/evaluation
train_datesplit.csv, test_datesplit.csv: Date-based splits to avoid data leakage

pubmed/

experimental_evidence.csv

PubMed abstracts associated with evidence entries
Links evidence to published literature

VCI/ - Variant Curation Interface Data

Contains data for variant pathogenicity assessment tasks.

Core Files

clingen_vci_pubmed_fulltext.csv

Complete VCI dataset with full-text papers
Columns:
- entry_index: Unique identifier
- variant: HGVS variant notation
- hgnc_gene: Gene symbol
- disease: Associated disease
- mondo_id: MONDO disease identifier
- assertion: Pathogenicity classification (Pathogenic, Likely Pathogenic, Uncertain Significance, etc.)
- mode_inheritance: Inheritance pattern
- expert_panel: Responsible VCEP (Variant Curation Expert Panel)
- pub_date: Publication date
- evidence_code: ACMG/AMP evidence code applied
- met_status: Whether evidence criteria was met
- pmid: Associated PubMed ID
- comments: Curator comments
- summary: Evidence summary
- summary_comments: Additional summary information

Data Variants:

clingen_vci_pubmed_fulltext_dedup_pmid.csv: Deduplicated by PMID
clingen_vci_pubmed_fulltext_vceps.csv: VCEP-specific subset
clingen_vci_pubmed_var_na_filtered.csv: Filtered for missing variants

erepo.tabbed_2025-02-25.txt

Raw ClinGen Evidence Repository export
Tab-delimited format with comprehensive variant classification data
Key Columns:
- #Variation: Variant identifier
- ClinVar Variation Id: ClinVar identifier
- HGVS Expressions: All HGVS representations
- Applied Evidence Codes (Met/Not Met): ACMG/AMP criteria
- Summary of interpretation: Detailed reasoning
- Expert Panel: Responsible VCEP

pubmed_id_to_text.csv

Maps PubMed IDs to full-text content
Columns:
- pmid: PubMed identifier
- abstract: Paper abstract
- full_text: Complete paper text when available

Task-Specific Splits

split_evidence_score/ Evidence scoring task data:

train.csv, test.csv: Basic train/test splits
train_merged.csv, test_merged.csv: Merged with additional metadata
Additional path column indicates source VCEP specification file

split_evidence_sufficiency/ Evidence sufficiency determination task:

train.csv, test.csv: Basic splits
train_dedup.csv, test_dedup.csv: Deduplicated versions
test_dedup_missing.csv: Test set with missing data scenarios

parsing_csr_criteria/

Contains tools and data for parsing Criteria Specification Registry (CSR) documents:

cspec_version_guide.csv: Maps VCEP specifications to versions
cspec_version_guide_processed.csv: Processed version mappings
version_csv_individual/: Individual CSV files for each VCEP specification version
- Format: {VCEPName}_version={X.Y.Z}.csv
- Contains parsed criteria specifications for each expert panel

Python Scripts:

get_versions.py: Extract version information
parse_on_date.py: Parse specifications by date
scrape_criteria.py: Scrape criteria from registry
scrape_criteria_fn.py, scrape_criteria_versions.py: Helper functions

Data Usage Notes

Evidence Codes

The dataset uses ACMG/AMP variant interpretation guidelines with evidence codes like:

PVS1: Very strong pathogenic evidence
PS1-4: Strong pathogenic evidence
PM1-6: Moderate pathogenic evidence
PP1-5: Supporting pathogenic evidence
BA1: Stand-alone benign
BS1-4: Strong benign evidence
BP1-7: Supporting benign evidence

Expert Panels (VCEPs)

Various disease-specific Variant Curation Expert Panels contribute data:

Phenylketonuria VCEP (PAH gene)
Cardiomyopathy VCEP
BRCA1/BRCA2 VCEP (ENIGMA)
And many others

Data Splits

Standard splits: Random train/test division
Date splits: Temporal division to prevent data leakage
Deduplicated versions: Remove duplicate entries by PMID or other criteria

File Formats

CSV: Comma-separated values for tabular data
JSON: Structured data for evidence category definitions
TXT: Tab-delimited raw exports from ClinGen systems

Citation

If you use this dataset, please cite the CGBench paper (publication details forthcoming).

License

MIT License - see main repository for details.

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