ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.38_39insCCCA (p.Glu13fs) (rs63750057)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075695 SCV000106681 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
GeneDx RCV000479728 SCV000566197 pathogenic not provided 2018-08-27 criteria provided, single submitter clinical testing This insertion of 4 nucleotides in MLH1 is denoted c.38_39insCCCA at the cDNA level and p.Glu13AspfsX19 (E13DfsX19) at the protein level. The normal sequence, with the bases that are inserted in brackets, is ACGA[CCCA]GACA. The insertion causes a frameshift, which changes a Glutamic Acid to an Aspartic Acid at codon 13, and creates a premature stop codon at position 19 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. MLH1 c.38_39insCCCA has been observed in a proband with a history of three metachronous colorectal cancers, whose family met Amsterdam Lynch Syndrome criteria (Rey 2004). we consider this variant to be pathogenic.

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