Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
All of Us Research Program, |
RCV004012885 | SCV004837756 | uncertain significance | Hypercholesterolemia, autosomal dominant, 3 | 2023-11-02 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with aspartic acid at codon 32 of the PCSK9 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different missense variant occurring at the same codon, p.Glu32Lys, reported to cause disease (ClinVar variation ID: 297692), indicating that glycine at this position is important for PCSK9 protein function. 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. |