ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.578del (p.Leu193fs) (rs587782281)

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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 RCV000162426 SCV000212773 pathogenic Hereditary cancer-predisposing syndrome 2017-11-07 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 RCV000480253 SCV000568719 pathogenic not provided 2017-11-09 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH6 is denoted c.578delT at the cDNA level and p.Leu193TrpfsX18 (L193WfsX18) at the protein level. The normal sequence, with the base that is deleted in braces, is GAAT[T]GGCA. The deletion causes a frameshift which changes a Leucine to a Tryptophan at codon 193, and creates a premature stop codon at position 18 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.578delT has been observed in at least one individual who had multi-gene panel testing due to a personal and/or family history suggestive of a hereditary cancer syndrome (LaDuca 2014). We consider this variant to be pathogenic.
Invitae RCV000231303 SCV000283849 pathogenic Hereditary nonpolyposis colon cancer 2018-09-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu193Trpfs*18) 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 reported in an individual undergoing hereditary cancer panel testing (PMID: 24763289). ClinVar contains an entry for this variant (Variation ID: 183724). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic.

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