ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1070C>T (p.Thr357Ile)

dbSNP: rs980612510
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000629851 SCV000750807 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-10-27 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PMS2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 357 of the PMS2 protein (p.Thr357Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine.
Color Diagnostics, LLC DBA Color Health RCV003584679 SCV004359638 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 357 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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