ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.872T>C (p.Leu291Pro)

gnomAD frequency: 0.00004  dbSNP: rs199999050
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000470696 SCV000547591 uncertain significance Colorectal cancer, susceptibility to, 10 2024-11-05 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 291 of the POLD1 protein (p.Leu291Pro). This variant is present in population databases (rs199999050, gnomAD 0.05%). This missense change has been observed in individual(s) with endometrial cancer (PMID: 26748215). ClinVar contains an entry for this variant (Variation ID: 408040). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV001753884 SCV001987877 uncertain significance not provided 2019-12-09 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in an individual with endometrial cancer (Wong 2016); This variant is associated with the following publications: (PMID: 26748215)
Ambry Genetics RCV004943888 SCV005476256 benign Hereditary cancer-predisposing syndrome 2024-08-20 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.

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