Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000236230 | SCV000294004 | uncertain significance | not provided | 2024-10-09 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25122428, 9545286, 29056344) |
| Labcorp Genetics |
RCV000475476 | SCV000547586 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2025-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 238 of the POLD1 protein (p.Thr238Met). This variant is present in population databases (rs553342844, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. 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: 246444). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Fulgent Genetics, |
RCV000764214 | SCV000895217 | uncertain significance | Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Institute for Clinical Genetics, |
RCV000236230 | SCV002010599 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004943824 | SCV005470076 | benign | Hereditary cancer-predisposing syndrome | 2024-10-28 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |