ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2356C>A (p.Leu786Met) (rs576055272)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131526 SCV000186520 likely benign Hereditary cancer-predisposing syndrome 2018-05-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,Subpopulation frequency in support of benign classification
CeGaT Praxis fuer Humangenetik Tuebingen RCV000656951 SCV000892766 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
Counsyl RCV000662644 SCV000785331 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2017-07-07 criteria provided, single submitter clinical testing
GeneDx RCV000656951 SCV000279150 uncertain significance not provided 2017-11-17 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.2356C>A at the cDNA level, p.Leu786Met (L786M) at the protein level, and results in the change of a Leucine to a Methionine (CTG>ATG). PMS2 Leu786Met was identified in at least one individual among a cohort of 145 patients who underwent PMS2 clinical testing, as well as in an individual with previously negative BRCA1/2 analysis (Vaughn 2010, Yadav 2016). Although this variant was observed in large population cohorts, population data in this region of PMS2 are not considered reliable due to high pseudogene homology (Lek 2016). PMS2 Leu786Met is located in the Endonuclease domain (Fukui 2011). In-silico analysis, including protein predictors and evolutionary conservation, supports that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether PMS2 Leu786Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GeneKor MSA RCV000131526 SCV000822132 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000198951 SCV000255292 benign Hereditary nonpolyposis colon cancer 2017-06-23 criteria provided, single submitter clinical testing
PreventionGenetics RCV000218670 SCV000304731 likely benign not specified criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000218670 SCV000601844 benign not specified 2017-07-04 criteria provided, single submitter clinical testing

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