Genes in panel
STRs in panel
Prev Next

Undiagnosed metabolic disorders

Gene: PCSK9

Green List (high evidence)

PCSK9 (proprotein convertase subtilisin/kexin type 9)
EnsemblGeneIds (GRCh38): ENSG00000169174
EnsemblGeneIds (GRCh37): ENSG00000169174
OMIM: 607786, Gene2Phenotype
PCSK9 is in 6 panels

1 review

Sarah Leigh (Genomics England Curator)

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, 2:30 p.m. | Last Modified: 19 Aug 2019, 2:30 p.m.
Panel Version: 1.227
Comment on list classification: 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: 1.226
Comment on phenotypes: (Inherited hypercholesterolaemias)
Created: 19 Aug 2019, 2:12 p.m. | Last Modified: 19 Aug 2019, 2:12 p.m.
Panel Version: 1.224
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)
Created: 6 Jan 2017, 2:01 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Familial hypercholesterolaemia

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Hypercholesterolemia, familial, 3 603776
  • {Low density lipoprotein cholesterol level QTL 1} 603776
OMIM
607786
Clinvar variants
Variants in PCSK9
Penetrance
Complete
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
Panels with this gene

History Filter Activity

19 Aug 2019, Gel status: 3

Set mode of pathogenicity

Sarah Leigh (Genomics England Curator)

Mode of pathogenicity for gene: PCSK9 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

19 Aug 2019, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pcsk9 has been classified as Green List (High Evidence).

19 Aug 2019, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PCSK9 were set to 27604308

19 Aug 2019, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: PCSK9 were changed from Autosomal dominant hypercholesterolemia-3 (Inherited hypercholesterolaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 603776

27 Feb 2017, Gel status: 2

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Construction of “Undiagnosed Metabolic Disorders” (UDM) panel • The 614 genes from the neurometabolic gene panel (PMID: 27604308) added • Green genes downloaded from V1 metabolic panels (Cerebral folate deficiency, Congenital disorders of glycosylation, Hyperammonaemia, Ketotic hypoglycaemia, Mitochondrial disorders, Mucopolysaccharideosis, Gaucher, Fabry, Peroxisomal disorders), sources replaced with "Expert review green", then loaded as a review onto UDM panel, resulting in 367 green genes and 333 red (therefore 86 new green genes included from the additional metabolic panels that weren't previously on the UDM panel) • Downloaded green genes from all panels. Removed genes from none V1 panels. Removed genes from the metabolic panels mentioned above. Compared the remaining genes with the red genes from UDM panel. Loaded as an "Expert review Amber" review to the overlapping genes, (the panel name where the genes came from was used as the phenotype) • Used variant information from PMID 27604308 to review the genes on this panel • Reviewed genes on UDM panel with genes from Emory "Inherited Metabolic Disorders: Sequencing Panel" and UKGTN “Inborn Errors of Metabolism 226 panel”, changing status where appropriate, added 14 UKGTN genes that had not be listed before • Review 10 red genes that had not previously been reviewed, 4/10 were reclassified as green • Review the remaining 145 red genes that had not previously been reviewed (shared between reviewers EM, RF, LD, AT, HB, ON & SL), resulting in 60 green, 11 amber, 70 red, 4 I don’t know reviews) • Reviewed genes from PMID: 24816252 as a publication to genes found in the Inborn error or metabolism Genes metabolomics GWAS paper (figure 5). 2 new genes added

6 Jan 2017, Gel status: 2

Set Mode of Inheritance, Added New Source

Sarah Leigh (Genomics England Curator)

PCSK9 was added to Undiagnosed metabolic disorderspanel. Source: Expert Review Amber Model of inheritance for gene PCSK9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

28 Oct 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

PCSK9 was created by sleigh

28 Oct 2016, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

PCSK9 was added to Undiagnosed metabolic disorderspanel. Sources: Literature