ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1294C>G (p.Arg432Gly)

dbSNP: rs774130423
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000462290 SCV000547501 uncertain significance Colorectal cancer, susceptibility to, 10 2024-07-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 432 of the POLD1 protein (p.Arg432Gly). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 407957). 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.
Fulgent Genetics, Fulgent Genetics RCV000764219 SCV000895222 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010805 SCV001171054 likely benign Hereditary cancer-predisposing syndrome 2024-10-29 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Sema4, Sema4 RCV001010805 SCV002534576 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-18 criteria provided, single submitter curation
GeneDx RCV003441871 SCV004168064 uncertain significance not provided 2023-10-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20951805)
Baylor Genetics RCV000462290 SCV005056525 uncertain significance Colorectal cancer, susceptibility to, 10 2024-02-23 criteria provided, single submitter clinical testing

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