ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3743_3744insT (p.Tyr1249fs) (rs786201084)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162579 SCV000212995 pathogenic Hereditary cancer-predisposing syndrome 2017-06-27 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)
Center for Human Genetics, Inc RCV000659896 SCV000781794 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2016-11-01 criteria provided, single submitter clinical testing
Color RCV000162579 SCV000690393 pathogenic Hereditary cancer-predisposing syndrome 2017-09-27 criteria provided, single submitter clinical testing
GeneDx RCV000479814 SCV000566320 pathogenic not provided 2017-08-09 criteria provided, single submitter clinical testing This insertion of one nucleotide in MSH6 is denoted c.3743_3744insT at the cDNA level and p.Tyr1249LeufsX26 (Y1249LfsX26) at the protein level. The normal sequence, with the base that is inserted in brackets, is CTCA[T]CTAC. The insertion causes a frameshift, which changes a Tyrosine to a Leucine at codon 1249, and creates a premature stop codon at position 26 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.
Invitae RCV000630201 SCV000751157 pathogenic Hereditary nonpolyposis colon cancer 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr1249Leufs*26) 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: 183794). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.

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