ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.229G>A (p.Glu77Lys) (rs751235177)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215049 SCV000274188 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-04 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000463790 SCV000552070 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 77 of the PMS2 protein (p.Glu77Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs751235177, ExAC 0.002%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 230591). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The lysine 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.
Counsyl RCV000662890 SCV000785804 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2017-12-05 criteria provided, single submitter clinical testing

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