ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1667C>T (p.Thr556Ile)

gnomAD frequency: 0.00001  dbSNP: rs1199212284
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001226246 SCV001398552 uncertain significance not provided 2024-10-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 556 of the MSH3 protein (p.Thr556Ile). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 953889). 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 RCV002402709 SCV002706602 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-15 criteria provided, single submitter clinical testing The p.T556I variant (also known as c.1667C>T), located in coding exon 12 of the MSH3 gene, results from a C to T substitution at nucleotide position 1667. The threonine at codon 556 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003462773 SCV004196995 uncertain significance Endometrial carcinoma 2023-10-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005040051 SCV005666190 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-05-14 criteria provided, single submitter clinical testing

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