Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001010990 | SCV001171264 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-29 | criteria provided, single submitter | clinical testing | The p.Q440H variant (also known as c.1320G>C), located in coding exon 10 of the POLD1 gene, results from a G to C substitution at nucleotide position 1320. The glutamine at codon 440 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. |
Invitae | RCV001050552 | SCV001214667 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2022-09-20 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs780771892, gnomAD 0.006%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 440 of the POLD1 protein (p.Gln440His). 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: 818913). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. |