Likely inborn error of metabolism

Gene: PCSK9

Green List (high evidence)

Monoallelic mode of inheritance is appropriate for PCSK9, as there is only one published report of biallelic PCSK9 in a patient with familial hypercholesterolemia (FH) (PMID: 26541928). In this case, the patient did not exhibit the features of homozygous FH and her clinical features were similar to her heterozygous parents (personal communication from: Mafalda Bourbon, Department of Health Promotion & Prevention of Non-Transmissive Diseases, National Institute of Health Doutor Ricardo Jorge, Portugal).

Created: 2 Sep 2024, 4:14 p.m. | Last Modified: 2 Sep 2024, 4:14 p.m.

Panel Version: 6.1

Comment on mode of pathogenicity: Gain of function variants are responsible for Hypercholesterolemia, familial, 3 603776, while loss of function variants are responsible for {Low density lipoprotein cholesterol level QTL 1} 603776.

Created: 19 Aug 2019, 2:31 p.m. | Last Modified: 19 Aug 2019, 2:31 p.m.

Panel Version: 1.215

Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 gain of function variants reported in unrelated cases of Hypercholesterolemia, familial, 3 603776 and at least 5 loss of function variants have been reported in unrelated cases of {Low density lipoprotein cholesterol level QTL 1} 603776.

Created: 19 Aug 2019, 2:29 p.m. | Last Modified: 19 Aug 2019, 2:29 p.m.

Panel Version: 1.214

Comment on phenotypes: (Inherited hypercholesterolaemias)

Created: 19 Aug 2019, 2:11 p.m. | Last Modified: 19 Aug 2019, 2:11 p.m.

Panel Version: 1.212

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown