Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Revvity Omics, |
RCV001782586 | SCV002021640 | likely pathogenic | Hypercholesterolemia, autosomal dominant, 3 | 2021-07-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001782586 | SCV002220029 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2021-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 106 of the PCSK9 protein (p.Gly106Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with hypocholesterolemia (PMID: 16424354, 18266662, 18710658). 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 expected to disrupt PCSK9 protein function. Experimental studies have shown that this missense change affects PCSK9 function (PMID: 16571601). 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. |
| All of Us Research Program, |
RCV001782586 | SCV004841148 | likely benign | Hypercholesterolemia, autosomal dominant, 3 | 2023-10-02 | criteria provided, single submitter | clinical testing |