ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1836dup (p.Leu613fs)

dbSNP: rs1669381138
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193125 SCV001361762 likely pathogenic Hereditary nonpolyposis colon cancer 2019-06-12 criteria provided, single submitter clinical testing Variant summary: MSH6 c.1836dupA (p.Leu613IlefsX27) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250650 control chromosomes. To our knowledge, no occurrence of c.1836dupA in individuals affected with Hereditary Non-Polyposis Colon Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001202838 SCV001373968 pathogenic Hereditary nonpolyposis colorectal neoplasms 2024-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu613Ilefs*27) 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: 928750). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002411724 SCV002716336 pathogenic Hereditary cancer-predisposing syndrome 2021-05-24 criteria provided, single submitter clinical testing The c.1836dupA pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of A at nucleotide position 1836, causing a translational frameshift with a predicted alternate stop codon (p.L613Ifs*27). 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. RCV003449626 SCV004188241 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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