ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.367C>T (p.Pro123Ser)

gnomAD frequency: 0.00002  dbSNP: rs761127022
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000461139 SCV000547515 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 123 of the POLD1 protein (p.Pro123Ser). This variant is present in population databases (rs761127022, gnomAD 0.004%). 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: 407970). 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 RCV001539753 SCV001757559 uncertain significance not provided 2024-03-21 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
MGZ Medical Genetics Center RCV000461139 SCV002580905 uncertain significance Colorectal cancer, susceptibility to, 10 2022-07-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348308 SCV002619163 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-27 criteria provided, single submitter clinical testing The p.P123S variant (also known as c.367C>T), located in coding exon 3 of the POLD1 gene, results from a C to T substitution at nucleotide position 367. The proline at codon 123 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GenomeConnect - Invitae Patient Insights Network RCV003483620 SCV004228770 not provided Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome; Adenomatous polyp of colon no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 02-22-2018 by Lab 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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