ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.257C>T (p.Ala86Val)

gnomAD frequency: 0.00004  dbSNP: rs148040399
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462279 SCV000547610 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-13 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 86 of the POLD1 protein (p.Ala86Val). This variant is present in population databases (rs148040399, 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: 408058). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759952 SCV000889671 uncertain significance not provided 2018-07-31 criteria provided, single submitter clinical testing
GeneDx RCV000759952 SCV001784705 uncertain significance not provided 2023-03-30 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as germline pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27149842)
Genetic Services Laboratory, University of Chicago RCV001821260 SCV002071644 uncertain significance not specified 2017-10-17 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV001535482 SCV001749415 not provided Mandibular hypoplasia-deafness-progeroid syndrome no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 03-10-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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