ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2587C>T (p.His863Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1244565898
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001248254 SCV001421725 uncertain significance Colorectal cancer, susceptibility to, 10 2023-07-17 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 863 of the POLD1 protein (p.His863Tyr). This variant is not present in population databases (gnomAD no frequency). 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: 972264). 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. 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 RCV002265018 SCV002546730 uncertain significance not provided 2022-06-29 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
Ambry Genetics RCV002451615 SCV002739187 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-20 criteria provided, single submitter clinical testing The p.H863Y variant (also known as c.2587C>T), located in coding exon 20 of the POLD1 gene, results from a C to T substitution at nucleotide position 2587. The histidine at codon 863 is replaced by tyrosine, 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.

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