ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2832_2833del (p.Ile944fs) (rs730881827)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000254666 SCV000884138 pathogenic not provided 2017-09-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000160743 SCV000215678 pathogenic Hereditary cancer-predisposing syndrome 2017-11-27 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)
Color RCV000160743 SCV000690296 pathogenic Hereditary cancer-predisposing syndrome 2017-07-24 criteria provided, single submitter clinical testing
Counsyl RCV000663331 SCV000786605 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2018-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000254666 SCV000211385 pathogenic not provided 2017-02-20 criteria provided, single submitter clinical testing This deletion of 2 nucleotides is denoted MSH6 c.2832_2833delAA at the cDNA level and p.Ile944MetfsX4 (I944MfsX4) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACAT[delAA]GAGA. The deletion causes a frameshift, which changes an Isoleucine to a Methionine at codon 944, and introduces a premature stop codon at position 4 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 RCV000464722 SCV000551100 pathogenic Hereditary nonpolyposis colon cancer 2018-09-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile944Metfs*4) 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 affected with endometrial cancer and colon polyps (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 182680). 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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