ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1628_1629del (p.Lys543fs)

dbSNP: rs587779219
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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) RCV000074672 SCV000107875 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV001383736 SCV001582989 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-01-11 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: 89209). This premature translational stop signal has been observed in individual(s) with breast cancer and with clinical features of Lynch syndrome (PMID: 20028993, 20215533). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys543Argfs*19) 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 RCV002399427 SCV002706071 pathogenic Hereditary cancer-predisposing syndrome 2023-06-27 criteria provided, single submitter clinical testing The c.1628_1629delAA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of two nucleotides at nucleotide positions 1628 to 1629, causing a translational frameshift with a predicted alternate stop codon (p.K543Rfs*19). This variant has been identified in the germline of one Australian Lynch syndrome family (Baglietto L et al. J. Natl. Cancer Inst., 2010 Feb;102:193-201) and one female with MSH6 deficient (by immunohistochemistry) breast cancer (Walsh MD et al. Clin. Cancer Res., 2010 Apr;16:2214-24). 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.
Myriad Genetics, Inc. RCV003450928 SCV004187214 pathogenic Lynch syndrome 5 2023-08-15 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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