ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1720C>G (p.Pro574Ala) (rs758018736)

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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 RCV000220236 SCV000274135 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-06 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000220236 SCV000686157 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-20 criteria provided, single submitter clinical testing
Invitae RCV000629788 SCV000750744 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 574 of the PMS2 protein (p.Pro574Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs758018736, ExAC 0.009%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 230549). 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.

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