ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3416del (p.Gly1139fs) (rs587781544)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129558 SCV000184339 pathogenic Hereditary cancer-predisposing syndrome 2017-10-30 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 RCV000657283 SCV000779014 pathogenic not provided 2018-05-17 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH6 is denoted c.3416delG at the cDNA level and p.Gly1139AlafsX6 (G1139AfsX6) at the protein level. The normal sequence, with the base that is deleted in brackets, is TGGGGG[delG]CAAG. The deletion causes a frameshift which changes a Glycine to an Alanine at codon 1139, and creates a premature stop codon at position 6 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH6 c.3416delG has been reported in an individual with Lynch syndrome (Morak 2017). We consider this variant to be pathogenic.
Invitae RCV000804902 SCV000944840 pathogenic Hereditary nonpolyposis colon cancer 2019-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly1139Alafs*6) 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 been observed in an individual with colorectal cancer (PMID: 28528517) and an individual undergoing testing for Lynch syndrome (PMID: 28514183). ClinVar contains an entry for this variant (Variation ID: 141166). 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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