ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.421A>G (p.Met141Val) (rs193922374)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212584 SCV000149440 uncertain significance not provided 2018-09-24 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.421A>G at the cDNA level, p.Met141Val (M141V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. The International Society for Gastrointestinal Hereditary Tumours Incorporated (InSiGHT) classifies this variant as being of uncertain significance based on insufficient evidence (Thompson 2014). MSH2 Met141Val was observed at an allele frequency of 0.08% (24/30780) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located in the Connector domain (Lutzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH2 Met141Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115531 SCV000186070 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-18 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV001079015 SCV000750968 likely benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000115531 SCV000904004 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000030254 SCV000052921 uncertain significance Lynch syndrome 2015-10-02 no assertion criteria provided clinical testing

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