Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001056141 | SCV001220562 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2020-08-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with POLD1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 1051 of the POLD1 protein (p.Phe1051Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. |
Ambry Genetics | RCV002320304 | SCV002610478 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-23 | criteria provided, single submitter | clinical testing | The p.F1051L variant (also known as c.3153C>G), located in coding exon 25 of the POLD1 gene, results from a C to G substitution at nucleotide position 3153. The phenylalanine at codon 1051 is replaced by leucine, an amino acid with highly 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. |