ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.643G>A (p.Val215Ile) (rs145959653)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197162 SCV000254332 uncertain significance Hereditary nonpolyposis colon cancer 2019-12-14 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 215 of the MSH6 protein (p.Val215Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs145959653, ExAC 0.02%). This variant was reported in an individual affected with serous endometrial cancer (PMID: 23104009). ClinVar contains an entry for this variant (Variation ID: 216321). General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD), and an algorithm developed specifically for the MSH6 gene (PMID: 23621914), suggest that this missense change is likely to be tolerated. However, these predictions have not been confirmed by published functional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000220344 SCV000276053 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-10 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Counsyl RCV000663025 SCV000786051 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2018-02-16 criteria provided, single submitter clinical testing
Color RCV000220344 SCV000903133 likely benign Hereditary cancer-predisposing syndrome 2016-01-07 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000582427 SCV000691918 uncertain significance not specified no assertion criteria provided clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761118 SCV000891034 uncertain significance B lymphoblastic leukemia lymphoma with t(12;21)(p13;q22); TEL-AML1 (ETV6-RUNX1) 2016-10-31 no assertion criteria provided clinical testing

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