ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3714_3715TA[1] (p.Ile1239fs) (rs1064794384)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561455 SCV000673947 pathogenic Hereditary cancer-predisposing syndrome 2016-04-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000482291 SCV000569026 pathogenic not provided 2015-12-21 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in MSH6 is denoted c.3716_3717delTA at the cDNA level and p.Ile1239LysfsX35 (I1239KfsX35) at the protein level. The normal sequence, with the bases that are deleted in braces, is ACTA[TA]AAAT. The deletion causes a frameshift, which changes an Isoleucine to a Lysine at codon 1239, and creates a premature stop codon at position 35 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Gharavi Laboratory,Columbia University RCV000482291 SCV000809467 pathogenic not provided 2018-09-16 no assertion criteria provided research
Invitae RCV000697841 SCV000826473 pathogenic Hereditary nonpolyposis colon cancer 2018-05-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile1239Lysfs*35) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. 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. ClinVar contains an entry for this variant (Variation ID: 420268). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000482291 SCV000778624 likely pathogenic not provided 2018-02-20 no assertion criteria provided clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000482291 SCV000889491 pathogenic not provided 2018-06-11 criteria provided, single submitter clinical testing

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