ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1819G>A (p.Val607Ile)

gnomAD frequency: 0.00001  dbSNP: rs786204109
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168042 SCV000218695 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 607 of the PMS2 protein (p.Val607Ile). This variant is present in population databases (rs786204109, gnomAD 0.003%). 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: 188154). 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 with a negative 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.
GeneDx RCV000482215 SCV000572229 uncertain significance not provided 2023-03-13 criteria provided, single submitter clinical testing Not observed at a 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
Ambry Genetics RCV000562276 SCV000670742 likely benign Hereditary cancer-predisposing syndrome 2019-01-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000562276 SCV000912092 likely benign Hereditary cancer-predisposing syndrome 2017-03-21 criteria provided, single submitter clinical testing

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