ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.683G>T (p.Gly228Val) (rs1554302319)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000540971 SCV000625675 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-04-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 228 of the PMS2 protein (p.Gly228Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PMS2-related disease. 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000589861 SCV000697357 uncertain significance not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.683G>T (p.Gly228Val) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 121412 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589861 SCV000889638 uncertain significance not provided 2017-09-20 criteria provided, single submitter clinical testing
Color RCV001178551 SCV001343017 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-19 criteria provided, single submitter clinical testing

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