ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1028G>A (p.Arg343His)

gnomAD frequency: 0.00003  dbSNP: rs140539427
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236082 SCV000293932 uncertain significance not provided 2021-11-22 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter 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)
Invitae RCV000540733 SCV000646449 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 343 of the POLD1 protein (p.Arg343His). This variant is present in population databases (rs140539427, 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: 246395). 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.
Ambry Genetics RCV000576104 SCV000670965 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-12 criteria provided, single submitter clinical testing The p.R343H variant (also known as c.1028G>A), located in coding exon 8 of the POLD1 gene, results from a G to A substitution at nucleotide position 1028. The arginine at codon 343 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Baylor Genetics RCV000540733 SCV004203481 uncertain significance Colorectal cancer, susceptibility to, 10 2023-08-10 criteria provided, single submitter clinical testing

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