ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.412G>C (p.Asp138His) (rs863224678)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196680 SCV000254612 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 138 of the PMS2 protein (p.Asp138His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. 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: 216457). 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 disruptive, 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.
Ambry Genetics RCV000215200 SCV000276910 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000215200 SCV000686202 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-30 criteria provided, single submitter clinical testing
Counsyl RCV000662394 SCV000784807 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2016-12-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759921 SCV000889628 uncertain significance not provided 2018-01-05 criteria provided, single submitter clinical testing

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