Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001182028 | SCV001347343 | likely benign | Familial hypercholesterolemia | 2019-01-08 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001876049 | SCV002193513 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2021-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 549 of the PCSK9 protein (p.Arg549His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs111400659, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with PCSK9-related conditions. ClinVar contains an entry for this variant (Variation ID: 922139). 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 PCSK9 protein function. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478714 | SCV004222370 | uncertain significance | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00023 (4/17522 chromosomes in African/African American subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| All of Us Research Program, |
RCV001876049 | SCV004845920 | likely benign | Hypercholesterolemia, autosomal dominant, 3 | 2023-11-28 | criteria provided, single submitter | clinical testing |