Submissions for variant NM_003072.5(SMARCA4):c.1076G>A (p.Arg359Gln)

gnomAD frequency: 0.00019  dbSNP: rs148530368

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000226681	SCV000285971	likely benign	Rhabdoid tumor predisposition syndrome 2	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000336152	SCV000410464	benign	Coffin-Siris syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV000571064	SCV000663871	likely benign	Hereditary cancer-predisposing syndrome	2018-08-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001582768	SCV001811004	uncertain significance	not provided	2021-05-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with a personal or family history including acute lymphoblastic leukemia (ALL) and other cancers (Zhang 2015, Wang 2017); This variant is associated with the following publications: (PMID: 26580448, 26353884, 23718828, 27363283)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001582768	SCV002010721	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001808589	SCV002056156	likely benign	Intellectual disability, autosomal dominant 16	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000571064	SCV002532361	likely benign	Hereditary cancer-predisposing syndrome	2021-06-28	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001582768	SCV004011010	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	SMARCA4: PP2, BS1
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001582768	SCV004220375	likely benign	not provided	2023-01-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003947754	SCV004763082	likely benign	SMARCA4-related disorder	2022-06-02	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).