Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000584317 | SCV000690976 | uncertain significance | Hypercholesterolemia, familial, 1 | 2017-10-23 | criteria provided, single submitter | clinical testing | Variant of Uncertain Significance due to insufficient evidence: Variant is located in the C-terminal, CM3 domain of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has the variant been reported in individuals affected with FH in the literature. This variant has been identified in 3/244444 chromosomes in the general population by the Genome Aggregation Database (gnomAD). In summary, available evidence is insufficient to determine the pathogenicity of this variant conclusively. |
Color Diagnostics, |
RCV000775303 | SCV000909562 | likely benign | Familial hypercholesterolemia | 2018-05-16 | criteria provided, single submitter | clinical testing | Likely Benign based on current evidence: This missense variant is located in the C-terminal, CM3 domain of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. This variant occurs in more than 10 mammalian species, suggesting that the variant is functionally tolerated. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has the variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 3/244444 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on available evidence, this variant is classified as Likely Benign. |
Ambry Genetics | RCV002420552 | SCV002720407 | uncertain significance | Cardiovascular phenotype | 2023-10-19 | criteria provided, single submitter | clinical testing | The p.V675I variant (also known as c.2023G>A), located in coding exon 12 of the PCSK9 gene, results from a G to A substitution at nucleotide position 2023. The valine at codon 675 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |