ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.207+2T>C (rs267607722)

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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) RCV000075508 SCV000106503 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507560 SCV000601385 likely pathogenic not provided 2016-10-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000153 SCV001156638 pathogenic not specified 2019-05-06 criteria provided, single submitter clinical testing The MLH1 c.207+2T>C variant (rs267607722) is reported in the literature in several individuals with a confirmed or suspected diagnosis of Lynch syndrome (Becouarn 2005, Bonadona 2011). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism, and it is reported as likely pathogenic by several laboratories, including an expert panel, in ClinVar (Variation ID: 90023). This variant abolishes the canonical splice donor site of intron 2, which is likely to disrupt gene function. Based on available information, this variant is considered to be likely pathogenic. References: Becouarn Y et al. Value of microsatellite instability typing in detecting hereditary non-polyposis colorectal cancer. A prospective multicentric study by the Association Aquitaine Gastro. Gastroenterol Clin Biol. 2005 Jun-Jul;29(6-7):667-75. Bonadona V et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011 Jun 8;305(22):2304-10.
Ambry Genetics RCV001014311 SCV001175005 pathogenic Hereditary cancer-predisposing syndrome 2018-03-27 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation

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