ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2127T>A (p.Tyr709Ter)

dbSNP: rs587779232
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074719 SCV000107927 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV000130308 SCV000185158 pathogenic Hereditary cancer-predisposing syndrome 2023-05-10 criteria provided, single submitter clinical testing The p.Y709* pathogenic mutation (also known as c.2127T>A), located in coding exon 4 of the MSH6 gene, results from a T to A substitution at nucleotide position 2127. This changes the amino acid from a tyrosine to a stop codon within coding exon 4. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Invitae RCV000690199 SCV000817878 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-10-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr709*) 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 premature translational stop signal has been observed in individual(s) with clinical features of MSH6-related conditions (PMID: 28514183). ClinVar contains an entry for this variant (Variation ID: 89255). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003148645 SCV003837478 pathogenic not provided 2023-10-18 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in an individual with ovarian cancer (Lilyquist et al., 2017); This variant is associated with the following publications: (PMID: 28152038, 28514183, 28888541)
Myriad Genetics, Inc. RCV003450942 SCV004188212 pathogenic Lynch syndrome 5 2023-08-16 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.
Baylor Genetics RCV003460669 SCV004196359 pathogenic Endometrial carcinoma 2021-08-28 criteria provided, single submitter clinical testing

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