Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690884 | SCV000818613 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1059*) in the POLD1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 amino acid(s) of the POLD1 protein. 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: 570099). 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 | RCV001018976 | SCV001180276 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-07-02 | criteria provided, single submitter | clinical testing | The p.Q1059* variant (also known as c.3175C>T), located in coding exon 25 of the POLD1 gene, results from a C to T substitution at nucleotide position 3175. This changes the amino acid from a glutamine to a stop codon within coding exon 25. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function via haploinsufficiency in POLD1 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |