ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2389A>T (p.Met797Leu)

dbSNP: rs1433888137
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000629727 SCV000750683 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-06-24 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 797 of the PMS2 protein (p.Met797Leu). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. 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: 525618). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function with a positive predictive value of 80%. 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.
Counsyl RCV000662650 SCV000785337 uncertain significance Lynch syndrome 4 2017-07-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV001015369 SCV001176194 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-06 criteria provided, single submitter clinical testing The p.M797L variant (also known as c.2389A>T), located in coding exon 14 of the PMS2 gene, results from an A to T substitution at nucleotide position 2389. The methionine at codon 797 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Myriad Genetics, Inc. RCV000662650 SCV004019731 uncertain significance Lynch syndrome 4 2023-04-03 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Breakthrough Genomics, Breakthrough Genomics RCV004691958 SCV005188434 uncertain significance not provided criteria provided, single submitter not provided

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