Familial hypercholesterolaemia
Gene: PCSK9Comment on mode of pathogenicity: Needs a small curated list of missense gain-of-function variants.Created: 28 Jun 2016, 12:28 p.m.
On the Inherited Cardiac Condition Genes panel for Familial Hypercholesterolaemia reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.1007/s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 29.Created: 19 Feb 2016, 2:48 p.m.
Loss of function variants cause low cholesterol. A small list of specific missense mutations cause FH by gain-of-function mechanism (usually a severe phenotype).Created: 2 Dec 2015, 10:10 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
loss of function mutations cause low levels of LDL-c. FH is caused by Gain-of-function mutations
Mutations in PCSK9 are found in <2% of monogenic FH patients but are the most severely affected (LDL-~c highest)Created: 24 Nov 2015, 4:43 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hypercholesterolaemia; elevated LDL-Cholesterol
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for PCSK9 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for PCSK9 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
PCSK9 was added to Familial hypercholesterolaemiapanel. Source: UKGTN
PCSK9 was added to Familial hypercholesterolaemiapanel. Source: Emory Genetics Laboratory
Model of inheritance for gene PCSK9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
PCSK9 was added to Familial hypercholesterolaemiapanel. Source: Illumina TruGenome Clinical Sequencing Services
PCSK9 was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen
PCSK9 was added to Familial hypercholesterolaemiapanel. Sources: Eligibility statement prior genetic testing