ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2768dup (p.Thr924fs)

dbSNP: rs267608063
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074781 SCV000107991 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV001854279 SCV002243237 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-09-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89316). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 18301448). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr924Aspfs*11) 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).
Ambry Genetics RCV002433572 SCV002751934 pathogenic Hereditary cancer-predisposing syndrome 2020-08-17 criteria provided, single submitter clinical testing The c.2768dupA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of A at nucleotide position 2768, causing a translational frameshift with a predicted alternate stop codon (p.T924Dfs*11). This alteration, described as c.2768_2769insA, was identified in a patient with MSH6-deficient rectal cancer at age 30 (Steinke V et al. Eur. J. Hum. Genet. 2008 May;16:587-92). 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.
Myriad Genetics, Inc. RCV003450949 SCV004187340 pathogenic Lynch syndrome 5 2023-08-18 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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