Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001050788 | SCV001214912 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2023-10-08 | criteria provided, single submitter | clinical testing | This variant, c.43_44insTTG, is a complex sequence change that results in the deletion of proline and insertion of two amino acid(s) in the POLD1 protein (p.Pro15delinsLeuAla). 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: 847274). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV002327302 | SCV002626743 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-05-28 | criteria provided, single submitter | clinical testing | The c.43_44insTTG variant (also known as p.P15delinsLA), located in coding exon 1 of the POLD1 gene, results from an in-frame TTG insertion at nucleotide positions 43 to 44. This results in the replacement of the proline at codon 15 with the insertion of a leucine and an alanine. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |