ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.309C>A (p.Tyr103Ter)

dbSNP: rs1553410230
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662582 SCV000785204 likely pathogenic Lynch syndrome 5 2017-06-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001390324 SCV001592008 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-08-30 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr103*) 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). ClinVar contains an entry for this variant (Variation ID: 548749). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002325335 SCV002608195 pathogenic Hereditary cancer-predisposing syndrome 2021-08-18 criteria provided, single submitter clinical testing The p.Y103* pathogenic mutation (also known as c.309C>A), located in coding exon 2 of the MSH6 gene, results from a C to A substitution at nucleotide position 309. This changes the amino acid from a tyrosine to a stop codon within coding exon 2. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration has been identified in a patient with MSH6-deficient uterine cancer and a family history meeting Amsterdam II criteria (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV000662582 SCV004018459 pathogenic Lynch syndrome 5 2023-03-27 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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