Familial hypercholesterolaemia (GMS)
Gene: PCSK9Comment on phenotypes: This gene is also associated with {Low density lipoprotein cholesterol level QTL 1}, 603776Created: 2 Mar 2021, 1:27 p.m. | Last Modified: 2 Mar 2021, 1:27 p.m.
Panel Version: 1.8
Gene part of the Global Lipid Genetic Consortium 12-SNP LDL-C gene score calculation (Talmud et al, 2013, PMID:23433573).Created: 8 Oct 2019, 8:18 p.m. | Last Modified: 8 Oct 2019, 8:18 p.m.
Panel Version: 0.3
Comment 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
Phenotypes for gene: PCSK9 were changed from Hypercholesterolemia, familial, 3, 603776; Familial Hypercholesterolaemia; Hypercholesterolemia; {Low density lipoprotein cholesterol level QTL 1}, 603776; Familial Hypercholesterolemia to Hypercholesterolemia, familial, 3, OMIM:603776
gene: PCSK9 was added gene: PCSK9 was added to Familial hypercholesterolaemia - targeted panel. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Green,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory Mode of inheritance for gene: PCSK9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PCSK9 were set to 16224054; 23433573 Phenotypes for gene: PCSK9 were set to Hypercholesterolemia, familial, 3, 603776; Familial Hypercholesterolaemia; Hypercholesterolemia; {Low density lipoprotein cholesterol level QTL 1}, 603776; Familial Hypercholesterolemia Mode of pathogenicity for gene: PCSK9 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments