Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000775270 | SCV000909529 | uncertain significance | Familial hypercholesterolemia | 2023-03-29 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with methionine at codon 241 of the PCSK9 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PCSK9-related disorders in the literature; it has been reported in an individual with very circulating LDL-C (PMID: 24507775). This variant has been identified in 5/249048 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV000801433 | SCV000941209 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2025-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 241 of the PCSK9 protein (p.Val241Met). This variant is present in population databases (rs147478188, gnomAD 0.006%). This missense change has been observed in individual(s) with low LDL-C levels (PMID: 24507775). ClinVar contains an entry for this variant (Variation ID: 630150). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PCSK9 protein function with a positive predictive value of 80%. 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. |
| Fulgent Genetics, |
RCV000801433 | SCV002799593 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2022-02-17 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000801433 | SCV004842879 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2024-03-14 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with methionine at codon 241 of the PCSK9 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PCSK9-related disorders in the literature; it has been reported in an individual with very circulating LDL-C (PMID: 24507775). This variant has been identified in 5/249048 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |