ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.554A>G (p.Asp185Gly)

gnomAD frequency: 0.00011  dbSNP: rs144012714
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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 RCV000798455 SCV000938072 uncertain significance not provided 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 185 of the MSH3 protein (p.Asp185Gly). This variant is present in population databases (rs144012714, gnomAD 0.06%). 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: 644519). 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 tolerated. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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.
Sema4, Sema4 RCV002257959 SCV002536536 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-28 criteria provided, single submitter curation
Ambry Genetics RCV002257959 SCV002651750 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-14 criteria provided, single submitter clinical testing The p.D185G variant (also known as c.554A>G), located in coding exon 3 of the MSH3 gene, results from an A to G substitution at nucleotide position 554. The aspartic acid at codon 185 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003461103 SCV004197011 uncertain significance Endometrial carcinoma 2024-03-17 criteria provided, single submitter clinical testing
GeneDx RCV000798455 SCV005626675 uncertain significance not provided 2024-07-12 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005036154 SCV005673166 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-05-23 criteria provided, single submitter clinical testing

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