ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2690dup (p.Asn897fs) (rs1553414010)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000503246 SCV000592612 pathogenic Lynch syndrome 2016-06-30 criteria provided, single submitter clinical testing
GeneDx RCV000483177 SCV000568720 pathogenic not provided 2017-09-06 criteria provided, single submitter clinical testing This duplication of one nucleotide in MSH6 is denoted c.2690dupA at the cDNA level and p.Asn897LysfsX3 (N897KfsX3) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CAAAAA[dupA]TCCT. The duplication causes a frameshift which changes an Asparagine to a Lysine at codon 897, and creates a premature stop codon at position 3 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.2690dupA has been observed in at least one family with Lynch syndrome and in at least one individual with ovarian cancer (Baglietto 2010, Pal 2012). We consider this variant to be pathogenic.
Invitae RCV000696931 SCV000825514 pathogenic Hereditary nonpolyposis colon cancer 2018-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn897Lysfs*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 been observed in individuals affected with Lynch syndrome-associated cancers (PMID: 20028993, Invitae) and with ovarian cancer (PMID: 23047549). This variant is also known as c.2690_2691insA in the literature. ClinVar contains an entry for this variant (Variation ID: 420121). 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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