ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3379_3438+5del (rs1553331676)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074844 SCV000108056 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon (also interrupts canonical donor splice site)
GeneDx RCV000214789 SCV000279555 pathogenic not provided 2015-11-11 criteria provided, single submitter clinical testing This deletion of 65 nucleotides in MSH6 is denoted c.3379_3438+5del65 at the cDNA level and p.Ala1127LeufsX15 (A1127LfsX15) at the protein level. The surrounding sequence is CAAA[del65]tgat, where the capital letters are exonic and lowercase are intronic. The deletion causes a frameshift, which changes an Alanine to a Leucine at codon 1127, and creates a premature stop codon at position 15 of the new reading frame. This variant is predicted to cause loss of normal protein function through protein truncation and to destroy a canonical splice donor site resulting in abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. MSH6 c.3379_3438+5del65 has been reported in at least one individual with early onset colon cancer and a family history consistent with Lynch syndrome and the International Society for Gastrointestinal Hereditary Tumours Incorporated (InSiGHT) classifies this variant as pathogenic (Steinke 2008, Thompson 2014). We consider this variant to be pathogenic.
Ambry Genetics RCV000490849 SCV000580107 pathogenic Hereditary cancer-predisposing syndrome 2017-10-26 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)

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