ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.1561C>T (p.Arg521Trp)

dbSNP: rs2145942104
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001875324 SCV002148959 uncertain significance Rhabdoid tumor predisposition syndrome 2 2021-12-22 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with clinical features of Coffin-Siris syndrome (PMID: 31530938). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 521 of the SMARCA4 protein (p.Arg521Trp).
PreventionGenetics, part of Exact Sciences RCV003407895 SCV004108316 uncertain significance SMARCA4-related disorder 2023-06-13 criteria provided, single submitter clinical testing The SMARCA4 c.1561C>T variant is predicted to result in the amino acid substitution p.Arg521Trp. This variant was reported as de novo in an individual with Coffin-Siris syndrome (Sekiguchi et al. 2019. PubMed ID: 31530938). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GeneDx RCV004728902 SCV005334919 pathogenic not provided 2024-03-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30286321, 31530938, 24658002)

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