ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.644C>T (p.Ala215Val)

gnomAD frequency: 0.00001  dbSNP: rs993539085
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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 RCV000792190 SCV000931470 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 215 of the POLD1 protein (p.Ala215Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 639408). 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 RCV001592969 SCV001814604 uncertain significance not provided 2022-09-16 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005021191 SCV005650287 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome; Immunodeficiency 120 2024-03-24 criteria provided, single submitter clinical testing

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