ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3996_3999dup (p.Arg1334fs) (rs1553333753)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630092 SCV000751048 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-06-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MSH6 gene (p.Arg1334Ilefs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acids of the MSH6 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related disease. A different frameshift variant leading to a premature stop signal at the same codon (p.Leu1330Valfs*12) has been determined to be pathogenic (PMID: 19851887, 21155762). This suggests that the C-terminal region is critical for MSH6 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mendelics RCV000708896 SCV000837928 likely pathogenic Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000771471 SCV000903915 likely pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Mendelics RCV000986745 SCV001135857 likely pathogenic Hereditary nonpolyposis colorectal cancer type 5 2019-05-28 criteria provided, single submitter clinical testing

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