ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.187G>A (p.Glu63Lys)

gnomAD frequency: 0.00009  dbSNP: rs200736325
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472021 SCV000547528 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 63 of the POLD1 protein (p.Glu63Lys). This variant is present in population databases (rs200736325, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 407981). 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 POLD1 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 RCV001721498 SCV000572306 likely benign not provided 2019-07-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481133 SCV000601894 uncertain significance not specified 2017-05-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002525562 SCV003745311 likely benign Inborn genetic diseases 2022-06-29 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.
CeGaT Center for Human Genetics Tuebingen RCV001721498 SCV004183692 likely benign not provided 2023-12-01 criteria provided, single submitter clinical testing POLD1: BP4

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