ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1790G>A (p.Trp597Ter) (rs63750604)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075365 SCV000106359 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000075365 SCV000543557 pathogenic Lynch syndrome 2016-08-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 597 (p.Trp597*) of the MLH1 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). A different variant (c.1791del) giving rise to the same protein effect observed here (p.Trp597*) has been reported in a patient affected with Lynch syndrome (PMID: 21642682). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000479277 SCV000569941 pathogenic not provided 2016-04-08 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.1790G>A at the cDNA level and p.Trp597Ter (W597X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Ambry Genetics RCV000565193 SCV000676045 pathogenic Hereditary cancer-predisposing syndrome 2018-03-08 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000479277 SCV000778616 pathogenic not provided 2017-11-08 no assertion criteria provided clinical testing

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