Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486966 | SCV000572382 | uncertain significance | not provided | 2016-11-29 | criteria provided, single submitter | clinical testing | This variant is denoted POLD1 c.3221G>A at the cDNA level, p.Arg1074Gln (R1074Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. POLD1 Arg1074Gln was not observed at a significant allele frequency in 1000 Genomes. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. POLD1 Arg1074Gln occurs at a position that is conserved across species and is located in the zinc finger domains (Tahirov 2009). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether POLD1 Arg1074Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV000530844 | SCV000646640 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1074 of the POLD1 protein (p.Arg1074Gln). This variant is present in population databases (rs541931950, gnomAD 0.01%). 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: 422817). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Center for Genomic Medicine, |
RCV002465687 | SCV002761091 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing |