Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568173 | SCV000671164 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-24 | criteria provided, single submitter | clinical testing | The p.D496H variant (also known as c.1486G>C), located in coding exon 11 of the POLD1 gene, results from a G to C substitution at nucleotide position 1486. The aspartic acid at codon 496 is replaced by histidine, an amino acid with 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. |
| Invitae | RCV002528157 | SCV002967850 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-05-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 496 of the POLD1 protein (p.Asp496His). This variant is present in population databases (rs777809352, gnomAD 0.004%). ClinVar contains an entry for this variant (Variation ID: 484398). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |