ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.999del (p.Lys334fs) (rs1060502932)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522846 SCV000618302 pathogenic not provided 2017-02-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH6 is denoted c.999delC at the cDNA level and p.Lys334ArgfsX4 (K334RfsX4) at the protein level. The normal sequence, with the base that is deleted in brackets, is AAAC[delC]AAGA. The deletion causes a frameshift which changes a Lysine to an Arginine at codon 334, and creates 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 RCV000456722 SCV000551242 pathogenic Lynch syndrome 2016-07-31 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 4 of the MSH6 mRNA (c.999delC), causing a frameshift at codon 334. This creates a premature translational stop signal (p.Lys334Argfs*4) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, 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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