ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1507T>G (p.Ser503Ala) (rs864622497)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204159 SCV000260856 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-24 criteria provided, single submitter clinical testing This sequence change replaces serine with alanine at codon 503 of the PMS2 protein (p.Ser503Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 220368). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Color RCV000583752 SCV000691024 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-10 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679351 SCV000806175 uncertain significance not provided 2017-12-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780616 SCV000918035 uncertain significance not specified 2017-09-19 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.1507T>G (p.Ser503Ala) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 277128 control chromosomes. In literature, this variant is reported in one individual with invasive breast carcinoma without strong evidence for or against pathogenicity (Balogh_2006). Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
Ambry Genetics RCV000583752 SCV001172332 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-14 criteria provided, single submitter clinical testing Insufficient evidence

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