Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000233864 | SCV000287505 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 386 of the POLD1 protein (p.Arg386His). This variant is present in population databases (rs764023083, gnomAD 0.01%). 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: 239224). 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. |
| Ambry Genetics | RCV000563945 | SCV000670957 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-18 | criteria provided, single submitter | clinical testing | The p.R386H variant (also known as c.1157G>A), located in coding exon 9 of the POLD1 gene, results from a G to A substitution at nucleotide position 1157. The arginine at codon 386 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well 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. |
| Laboratory for Molecular Medicine, |
RCV000602237 | SCV000712905 | uncertain significance | not specified | 2017-03-09 | criteria provided, single submitter | clinical testing | The p.Arg386His variant in POLD1 has not been previously reported in individuals with colorectal cancer, but has been reported by other clinical laboratories in ClinVar (Variation ID 239224). It has been identified in 2/30782 South Asian ch romosomes and 1/9850 Ashkenazi Jewish chromosomes by the Genome Aggregation Data base (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs764023083). Computationa l prediction tools and conservation analysis suggest that the p.Arg386His varian t may not impact the protein, though this information is not predictive enough t o rule out pathogenicity. In summary, the clinical significance of the p.Arg386H is variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4. |
| Fulgent Genetics, |
RCV000764217 | SCV000895220 | uncertain significance | Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001589181 | SCV001826756 | uncertain significance | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 29056344, 20951805) |
| Center for Genomic Medicine, |
RCV000602237 | SCV002761053 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000233864 | SCV004203479 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-08-20 | criteria provided, single submitter | clinical testing |