ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1753C>A (p.Leu585Ile) (rs63750947)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216706 SCV000278562 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000427927 SCV000518107 likely benign not specified 2017-08-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000524448 SCV000552041 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 585 of the PMS2 protein (p.Leu585Ile). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is present in population databases (rs63750947, ExAC 0.002%). This variant has been reported in individuals with suspected Lynch syndrome (PMID: 16472587, 27435373) and colorectal cancer (PMID: 28135145). However, in some of these individuals, the variant was on the same chromosome (in cis) with a pathogenic variant (p.Arg628*) in the PMS2 gene. ClinVar contains an entry for this variant (Variation ID: 91313). In an experimental study, this variant did not have a significant effect on mismatch repair activity compared to wild-type PMS2 (PMID: 24027009). 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 RCV000216706 SCV000911785 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-06 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000216706 SCV000788109 likely benign Hereditary cancer-predisposing syndrome 2017-07-31 no assertion criteria provided clinical testing

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