ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1706A>G (p.Glu569Gly) (rs786201077)

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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 RCV000162561 SCV000212972 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-09 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000168102 SCV000218758 uncertain significance Hereditary nonpolyposis colon cancer 2019-11-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 569 of the MSH2 protein (p.Glu569Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an affected individual in the Universal Mutation Database (PMID: 22144684). ClinVar contains an entry for this variant (Variation ID: 183783). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV000585899 SCV000696224 uncertain significance not specified 2019-11-05 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1706A>G (p.Glu569Gly) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, core domain (IPR007696) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250804 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1706A>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported in the literature. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Counsyl RCV000663034 SCV000786070 uncertain significance Lynch syndrome I 2018-02-15 criteria provided, single submitter clinical testing
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761166 SCV000891082 uncertain significance Papillary thyroid carcinoma 2017-04-26 no assertion criteria provided clinical testing

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