ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.382C>T (p.Arg128Cys)

dbSNP: rs1251938412
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000551898 SCV000624929 likely benign Hereditary nonpolyposis colorectal neoplasms 2022-11-06 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000776879 SCV000912545 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000776879 SCV002621630 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-01 criteria provided, single submitter clinical testing The p.R128C variant (also known as c.382C>T), located in coding exon 2 of the MSH6 gene, results from a C to T substitution at nucleotide position 382. The arginine at codon 128 is replaced by cysteine, an amino acid with highly dissimilar 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153678 SCV003843169 uncertain significance Lynch syndrome 5 2022-11-29 criteria provided, single submitter clinical testing The MSH6 c.382C>T (p.Arg128Cys) missense change has a maximum subpopulation frequency of 0.00088% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Lynch syndrome or CMMRD. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
GeneDx RCV003226937 SCV003923976 uncertain significance not provided 2025-01-21 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29760388)

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