ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1180A>G (p.Lys394Glu)

dbSNP: rs1583323711
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000987837 SCV001137306 uncertain significance Lynch syndrome 4 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001858679 SCV002288249 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 394 of the PMS2 protein (p.Lys394Glu). 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: 802294). 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 not expected to disrupt PMS2 protein function. 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 RCV002337045 SCV002635268 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-08 criteria provided, single submitter clinical testing The p.K394E variant (also known as c.1180A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1180. The lysine at codon 394 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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