ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1847C>G (p.Ser616Cys) (rs772363120)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575424 SCV000662410 likely benign Hereditary cancer-predisposing syndrome 2017-08-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
Color RCV000575424 SCV000908382 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-04 criteria provided, single submitter clinical testing
Counsyl RCV000410099 SCV000489415 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2016-10-03 criteria provided, single submitter clinical testing
Invitae RCV000524121 SCV000283732 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 616 of the MSH6 protein (p.Ser616Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs772363120, ExAC 0.04%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 224580). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
University of Washington Department of Laboratory Medicine,University of Washington RCV000210205 SCV000266203 uncertain significance Lynch syndrome 2015-11-20 criteria provided, single submitter clinical testing

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