Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000229817 | SCV000287641 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 201 of the POLD1 protein (p.Tyr201His). 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: 239359). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985940 | SCV001134665 | uncertain significance | not provided | 2018-09-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000985940 | SCV002559555 | uncertain significance | not provided | 2023-09-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as germline pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29056344) |
| Ambry Genetics | RCV003165625 | SCV003912571 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-11 | criteria provided, single submitter | clinical testing | The p.Y201H variant (also known as c.601T>C), located in coding exon 5 of the POLD1 gene, results from a T to C substitution at nucleotide position 601. The tyrosine at codon 201 is replaced by histidine, an amino acid with 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. |