ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.2135G>A (p.Trp712Ter) (rs63750561)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075550 SCV000106547 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon with functional domain
Color RCV000581002 SCV000684800 pathogenic Hereditary cancer-predisposing syndrome 2016-12-15 criteria provided, single submitter clinical testing
Invitae RCV000686456 SCV000813975 pathogenic Hereditary nonpolyposis colon cancer 2018-12-04 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MLH1 gene (p.Trp712*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acids of the MLH1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Lynch syndrome (PMID: 8574961, 12810663, 20233461, 12624141,15855432). ClinVar contains an entry for this variant (Variation ID: 90065). A different truncation downstream of this variant (p.Tyr750*) has been determined to be pathogenic (PMID: 10422993, 16338176, 20533529). This suggests that deletion of the C-terminal region of the MLH1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202047 SCV000257087 pathogenic not provided no assertion criteria provided research

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