ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3982C>T (p.Gln1328Ter)

dbSNP: rs2104567084
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV001784680 SCV002017578 pathogenic not provided 2019-03-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002359254 SCV002623162 pathogenic Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing The p.Q1328* pathogenic mutation (also known as c.3982C>T), located in coding exon 9 of the MSH6 gene, results from a C to T substitution at nucleotide position 3982. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003451930 SCV004185652 pathogenic Lynch syndrome 5 2023-08-28 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Color Diagnostics, LLC DBA Color Health RCV002359254 SCV004357778 pathogenic Hereditary cancer-predisposing syndrome 2022-05-06 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 9 of the MSH6 gene, creating a premature translation stop signal. This variant is predicted to escape nonsense-mediated decay and be expressed as a truncated protein. Although functional studies have not been reported, this variant is expected to disrupt the C-terminal MSH2 binding domain (PMID: 12019211). To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. In addition, downstream truncations are known to be disease-causing (ClinVar variation ID: 42472, 525790, 218076). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as Pathogenic.

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