ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1234A>G (p.Thr412Ala)

dbSNP: rs1038164521
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460036 SCV000547638 uncertain significance Colorectal cancer, susceptibility to, 10 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 412 of the POLD1 protein (p.Thr412Ala). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 408086). 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 RCV000569155 SCV000671110 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-06 criteria provided, single submitter clinical testing The p.T412A variant (also known as c.1234A>G), located in coding exon 9 of the POLD1 gene, results from an A to G substitution at nucleotide position 1234. The threonine at codon 412 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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.
PreventionGenetics, part of Exact Sciences RCV000679475 SCV000806461 uncertain significance not provided 2017-10-27 criteria provided, single submitter clinical testing
GeneDx RCV000679475 SCV004021677 uncertain significance not provided 2023-07-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant 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)

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