ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.532G>C (p.Gly178Arg)

dbSNP: rs140707092
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484189 SCV000569645 uncertain significance not provided 2023-10-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29056344, 35780178, 37105989, 32265515, 34326862)
Labcorp Genetics (formerly Invitae), Labcorp RCV000541905 SCV000646675 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 178 of the POLD1 protein (p.Gly178Arg). This variant is present in population databases (rs140707092, gnomAD 0.02%). 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: 420703). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484189 SCV000888469 uncertain significance not provided 2019-10-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004535513 SCV004113558 uncertain significance POLD1-related disorder 2023-01-26 criteria provided, single submitter clinical testing The POLD1 c.532G>C variant is predicted to result in the amino acid substitution p.Gly178Arg. This variant has been reported in three related individuals, two of which had bladder cancer (Wang et al. 2021. PubMed ID: 32265515). This variant has also been reported in tumor specimens (Table S2, Campbell et al. 2017. PubMed ID: 29056344). This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-50905324-G-C) and is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/420703/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004943919 SCV005470064 likely benign Hereditary cancer-predisposing syndrome 2024-08-29 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.
Fulgent Genetics, Fulgent Genetics RCV005018805 SCV005650282 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome; Immunodeficiency 120 2024-01-11 criteria provided, single submitter clinical testing

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