ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.203A>G (p.Lys68Arg) (rs863224620)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197369 SCV000254289 uncertain significance Hereditary nonpolyposis colon cancer 2019-01-13 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 68 of the MSH6 protein (p.Lys68Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. While this variant is not present in population databases (no rsID), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 216303). 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 arginine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on mRNA splicing and protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000563728 SCV000669895 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-18 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000563728 SCV000908339 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-16 criteria provided, single submitter clinical testing

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