ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2736G>A (p.Trp912Ter)

dbSNP: rs1572728472
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001016441 SCV001177399 pathogenic Hereditary cancer-predisposing syndrome 2022-01-11 criteria provided, single submitter clinical testing The p.W912* pathogenic mutation (also known as c.2736G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 2736. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. In one case control study, this alteration was detected in 1/2222 individuals with invasive epithelial ovarian cancer and 0/1528 matched controls. (Song H et al. Hum Mol Genet, 2014 Sep;23:4703-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV002549439 SCV003325631 pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-01-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp912*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 821737). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003455093 SCV004188186 pathogenic Lynch syndrome 5 2023-08-18 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.

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