ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.2177C>G (p.Ser726Ter) (rs864622457)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204293 SCV000260715 likely pathogenic Lynch syndrome 2015-09-19 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the MLH1 mRNA at codon 726 (p.Ser726*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated MLH1 protein. This variant is not present in population databases (ExAC no frequency). This variant is located in the last coding exon of MLH1. Although it has not been reported in the literature, deleterious truncations have been reported downstream of this position (PMID: 16616355, 10923051, 8646682) indicating that the missing part of the MLH1 gene product is required for MLH1 function. For these reasons, this variant has been classified as Likely Pathogenic.

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