ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3878_3881dup (p.Pro1295fs) (rs1553333500)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479515 SCV000565238 pathogenic not provided 2018-06-04 criteria provided, single submitter clinical testing This duplication of 4 nucleotides in MSH6 is denoted c.3878_3881dupCTTG at the cDNA level and p.Pro1295LeufsX3 (P1295LfsX3) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is GGAG[dupCTTG]TCCT. The duplication causes a frameshift, which changes a Proline to a Leucine at codon 1295 and creates a premature stop codon at position 3 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. Based on currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000695362 SCV000823857 pathogenic Hereditary nonpolyposis colon cancer 2018-02-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro1295Leufs*3) 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: 418332). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479515 SCV000889499 likely pathogenic not provided 2017-12-22 criteria provided, single submitter clinical testing

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