Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000545454 | SCV000646498 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-12-21 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt POLD1 protein function. ClinVar contains an entry for this variant (Variation ID: 469210). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is present in population databases (rs775734510, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 549 of the POLD1 protein (p.Arg549Cys). |
| Ambry Genetics | RCV003302856 | SCV003989472 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-07 | criteria provided, single submitter | clinical testing | The p.R549C variant (also known as c.1645C>T), located in coding exon 12 of the POLD1 gene, results from a C to T substitution at nucleotide position 1645. The arginine at codon 549 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |