ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1720C>T (p.Arg574Trp)

gnomAD frequency: 0.00004  dbSNP: rs771054581
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000800882 SCV000940624 uncertain significance not provided 2025-01-12 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 574 of the MSH3 protein (p.Arg574Trp). This variant is present in population databases (rs771054581, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 646569). 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. 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.
Ambry Genetics RCV001012845 SCV001173352 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-13 criteria provided, single submitter clinical testing The p.R574W variant (also known as c.1720C>T), located in coding exon 12 of the MSH3 gene, results from a C to T substitution at nucleotide position 1720. The arginine at codon 574 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Sema4, Sema4 RCV001012845 SCV002535977 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-14 criteria provided, single submitter curation
GeneDx RCV000800882 SCV002568719 uncertain significance not provided 2022-08-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV004569572 SCV005053613 uncertain significance Endometrial carcinoma 2024-02-26 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005392409 SCV006057934 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2021-05-13 criteria provided, single submitter clinical testing

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