ClinGen Dosage Sensitivity Curation Page

PCSK9

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
19191301 Nonsense mutations in PCSK9 appear to be polymorphic and confer susceptibility to low LDL cholesterol (hypocholesterolemia) whereas dominant missense mutations predispose to high LDL cholesterol.
15654334 African Americans carry two loss of function changes in PCSK9 with a combined frequency of 2%. These variants resulted in a 40% reduction in plasma levels of LDL cholesterol.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.