Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000465394 | SCV000547527 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 920 of the POLD1 protein (p.Asp920Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 407980). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Gene |
RCV000679503 | SCV000570450 | uncertain significance | not provided | 2020-05-18 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Preventiongenetics, |
RCV000679503 | SCV000806512 | uncertain significance | not provided | 2017-07-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002436418 | SCV002752160 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-31 | criteria provided, single submitter | clinical testing | The p.D920N variant (also known as c.2758G>A), located in coding exon 21 of the POLD1 gene, results from a G to A substitution at nucleotide position 2758. The aspartic acid at codon 920 is replaced by asparagine, an amino acid with highly 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. |