Submissions for variant NM_001374828.1(ARID1B):c.5773C>T (p.Arg1925Ter)

dbSNP: rs797045282

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000193164	SCV000246534	pathogenic	Coffin-Siris syndrome 1	2014-06-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000624857	SCV000741625	pathogenic	Inborn genetic diseases	2016-07-05	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269579	SCV001449667	pathogenic	not provided	2016-12-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001269579	SCV001826063	pathogenic	not provided	2022-04-20	criteria provided, single submitter	clinical testing	Nonsense variant in the C-terminus predicted to result in protein truncation as the last 448 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28191890, 25533962, 31243159, 30349098, 28191889, 31785789)
Genome-Nilou Lab	RCV000193164	SCV002054290	pathogenic	Coffin-Siris syndrome 1	2021-07-15	criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV000193164	SCV002521101	pathogenic	Coffin-Siris syndrome 1	2022-05-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region. The variant has been previously reported as de novo in a similarly affected individual (PMID: 25533962 ). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000210302 / PMID: 25533962 ). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001269579	SCV001743463	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001269579	SCV001959273	pathogenic	not provided		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000193164	SCV002818436	not provided	Coffin-Siris syndrome 1		no assertion provided	phenotyping only	Variant classified as Pathogenic and reported on 08-28-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Solve-RD Consortium	RCV000193164	SCV005091233	likely pathogenic	Coffin-Siris syndrome 1	2022-06-01	no assertion criteria provided	provider interpretation	Variant confirmed as disease-causing by referring clinical team
PreventionGenetics, part of Exact Sciences	RCV004725042	SCV005335838	pathogenic	ARID1B-related disorder	2024-04-25	no assertion criteria provided	clinical testing	The ARID1B c.5404C>T variant is predicted to result in premature protein termination (p.Arg1802*). This variant was reported de novo in at least four individuals with ARID1B-associated phenotypes (Table S4, Fitzgerald et al. 2015. PubMed ID: 25533962; Table S1, van der Sluijs et al. 2019. PubMed ID: 30349098; Melo Gomes et al. 2019. PubMed ID: 31243159). This variant has not been reported in a large population database, indicating this variant is rare. This variant resides in a large terminal exon and numerous downstream loss-of-function variants have been documented to be disease causing (Table S1, van der Sluijs et al. 2019. PubMed ID: 30349098). This variant is interpreted as pathogenic.