U.S. flag

An official website of the United States government

NM_174936.4(PCSK9):c.646T>C (p.Phe216Leu) AND Hypercholesterolemia, autosomal dominant, 3

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Feb 12, 2008
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000003008.12

Allele description [Variation Report for NM_174936.4(PCSK9):c.646T>C (p.Phe216Leu)]

NM_174936.4(PCSK9):c.646T>C (p.Phe216Leu)

Gene:
PCSK9:proprotein convertase subtilisin/kexin type 9 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p32.3
Genomic location:
Preferred name:
NM_174936.4(PCSK9):c.646T>C (p.Phe216Leu)
Other names:
F216L
HGVS:
  • NC_000001.11:g.55052400T>C
  • NG_009061.1:g.17854T>C
  • NM_001407240.1:c.769T>C
  • NM_001407241.1:c.646T>C
  • NM_001407242.1:c.646T>C
  • NM_001407243.1:c.589T>C
  • NM_001407244.1:c.646T>C
  • NM_001407245.1:c.454T>C
  • NM_001407246.1:c.271T>C
  • NM_001407247.1:c.646T>C
  • NM_174936.4:c.646T>CMANE SELECT
  • NP_001394169.1:p.Phe257Leu
  • NP_001394170.1:p.Phe216Leu
  • NP_001394171.1:p.Phe216Leu
  • NP_001394172.1:p.Phe197Leu
  • NP_001394173.1:p.Phe216Leu
  • NP_001394174.1:p.Phe152Leu
  • NP_001394175.1:p.Phe91Leu
  • NP_001394176.1:p.Phe216Leu
  • NP_777596.2:p.Phe216Leu
  • NP_777596.2:p.Phe216Leu
  • LRG_275t1:c.646T>C
  • LRG_275:g.17854T>C
  • LRG_275p1:p.Phe216Leu
  • NC_000001.10:g.55518073T>C
  • NM_174936.3:c.646T>C
  • NR_110451.2:n.305T>C
  • NR_110451.3:n.979T>C
  • NR_176318.1:n.620T>C
  • NR_176319.1:n.936T>C
  • NR_176320.1:n.1059T>C
  • NR_176321.1:n.936T>C
  • NR_176322.1:n.936T>C
  • NR_176323.1:n.936T>C
  • NR_176324.1:n.1198T>C
  • Q8NBP7:p.Phe216Leu
Protein change:
F152L; PHE216LEU
Links:
UniProtKB: Q8NBP7#VAR_017200; OMIM: 607786.0002; dbSNP: rs28942112
NCBI 1000 Genomes Browser:
rs28942112
Molecular consequence:
  • NM_001407240.1:c.769T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407241.1:c.646T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407242.1:c.646T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407243.1:c.589T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407244.1:c.646T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407245.1:c.454T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407246.1:c.271T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407247.1:c.646T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_174936.4:c.646T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypercholesterolemia, autosomal dominant, 3 (FHCL3)
Synonyms:
Familial hypercholesterolemia 3; Familial Hypercholesterolemia, Autosomal Dominant, 3
Identifiers:
MONDO: MONDO:0011369; MedGen: C1863551; OMIM: 603776

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000023166OMIM
no assertion criteria provided
Pathogenic
(Feb 12, 2008) 		germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000490155GeneReviews
no classification provided
not providedgermlineliterature only

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.

Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, et al.

Nat Genet. 2003 Jun;34(2):154-6.

PubMed [citation]
PMID:
12730697

Molecular basis for LDL receptor recognition by PCSK9.

Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J.

Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1820-5. doi: 10.1073/pnas.0712064105. Epub 2008 Feb 4.

PubMed [citation]
PMID:
18250299
PMCID:
PMC2538846

Details of each submission

From OMIM, SCV000023166.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In the proband of a family with autosomal dominant hypercholesterolemia-3 (FHCL3; 603776) who died from myocardial infarction at 49 years of age, Abifadel et al. (2003) identified an 890T-C transition in exon 4 of the PCSK9 gene, resulting in a phe216-to-leu (F216L) substitution.

Kwon et al. (2008) stated that phe216 is located within a disordered loop in PCSK9 and that the F216L mutation reduces proteolytic processing of PCSK9 after arg218.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From GeneReviews, SCV000490155.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature onlynot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024