ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1693T>G (p.Leu565Val)

dbSNP: rs786202870
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165917 SCV000216672 uncertain significance Hereditary cancer-predisposing syndrome 2025-03-01 criteria provided, single submitter clinical testing The c.1693T>G (p.L565V) alteration is located in exon 11 (coding exon 11) of the PMS2 gene. This alteration results from a T to G substitution at nucleotide position 1693, causing the leucine (L) at amino acid position 565 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000480451 SCV000565416 uncertain significance not provided 2022-11-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000531904 SCV000625552 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 565 of the PMS2 protein (p.Leu565Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 186338). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. 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.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000415672 SCV000493781 uncertain significance Lynch syndrome 4 2015-08-13 no assertion criteria provided clinical testing

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