ClinVar Miner

Submissions for variant NM_003073.5(SMARCB1):c.1120C>T (p.Arg374Trp)

dbSNP: rs1568963596
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000782071 SCV000920541 pathogenic not provided 2018-12-26 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002290029 SCV002579633 likely pathogenic Intellectual disability, autosomal dominant 15 2021-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000782071 SCV002588171 uncertain significance not provided 2022-04-22 criteria provided, single submitter clinical testing Observed in an individual with multiple schwannomas (Bellantoni et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33053319, Guan2016[Other], 30851333, 30555950)
Labcorp Genetics (formerly Invitae), Labcorp RCV000782071 SCV005781643 uncertain significance not provided 2024-05-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 374 of the SMARCB1 protein (p.Arg374Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with schwannomatosis (PMID: 30555950). ClinVar contains an entry for this variant (Variation ID: 633561). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg374 amino acid residue in SMARCB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23906836, 26364901, 31273213; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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