Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000457858 | SCV000547552 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-08-10 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 408005). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 858 of the POLD1 protein (p.Glu858Asp). |
| Victorian Clinical Genetics Services, |
RCV002470859 | SCV002769325 | uncertain significance | Mandibular hypoplasia-deafness-progeroid syndrome | 2020-05-21 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_001256849.1(POLD1):c.2574G>T in exon 21 of 27 of the POLD1 gene. This substitution is predicted to create a minor amino acid change from a glutamic acid to an aspartic acid at position 858 of the protein; NP_001243778.1(POLD1):p.(Glu858Asp). The glutamic acid at this position has low conservation (100 vertebrates, UCSC), but is located within the polymerase active site region (Weedon, M. N. et al. (2013)). In silico software predicts this variant to be tolerated (PolyPhen2, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database. This variant has been previously been reported as a VUS (ClinVar). Based on information available at the time of curation, this variant has been classified as a VUS with LOW CLINICAL RELEVANCE. Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |