ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.908dup (p.Met303fs) (rs1057517551)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411044 SCV000488242 likely pathogenic Hereditary nonpolyposis colorectal cancer type 5 2016-02-02 criteria provided, single submitter clinical testing
Invitae RCV000473148 SCV000551210 pathogenic Hereditary nonpolyposis colorectal neoplasms 2018-11-25 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 4 of the MSH6 mRNA (c.908dupT), causing a frameshift at codon 303. This creates a premature translational stop signal (p.Met303Ilefs*9) and 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 a MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 371820). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000482391 SCV000572163 pathogenic not provided 2016-10-31 criteria provided, single submitter clinical testing This duplication of one nucleotide in MSH6 is denoted c.908dupT at the cDNA level and p.Met303IlefsX9 (M303IfsX9) at the protein level. The normal sequence, with the base that is duplicated in braces, is AGAA[T]GGTG. The duplication causes a frameshift which changes a Methionine to an Isoleucine at codon 303, and creates a premature stop codon at position 9 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.
Ambry Genetics RCV000491372 SCV000580314 pathogenic Hereditary cancer-predisposing syndrome 2018-03-26 criteria provided, single submitter clinical testing The c.908dupT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a duplication of T at nucleotide position 908, causing a translational frameshift with a predicted alternate stop codon (p.M303Ifs*9). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000482391 SCV001134461 pathogenic not provided 2019-03-11 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.

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