Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001037485 | SCV001200900 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 271 of the POLD1 protein (p.Gly271Arg). 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: 836371). 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 with a negative predictive value of 80%. 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. |
Genetic Services Laboratory, |
RCV001819741 | SCV002064741 | uncertain significance | not specified | 2020-09-24 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the POLD1 gene demonstrated a sequence change, c.811G>A, in exon 7 that results in an amino acid change, p.Gly271Arg. This sequence change does not appear to have been previously described in patients with POLD1-related disorders and has also not been described in population databases (gnomAD, ExAC). The p.Gly271Arg change affects a highly conserved amino acid residue located in a domain of the POLD1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Gly271Arg substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Gly271Arg change remains unknown at this time. |