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NM_174936.4(PCSK9):c.10G>A (p.Val4Ile) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 25, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000583160.3

Allele description [Variation Report for NM_174936.4(PCSK9):c.10G>A (p.Val4Ile)]

NM_174936.4(PCSK9):c.10G>A (p.Val4Ile)

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.10G>A (p.Val4Ile)
HGVS:
  • NC_000001.11:g.55039847G>A
  • NG_009061.1:g.5301G>A
  • NM_174936.4:c.10G>AMANE SELECT
  • NP_777596.2:p.Val4Ile
  • NP_777596.2:p.Val4Ile
  • LRG_275t1:c.10G>A
  • LRG_275:g.5301G>A
  • LRG_275p1:p.Val4Ile
  • NC_000001.10:g.55505520G>A
  • NM_174936.3:c.10G>A
Protein change:
V4I
Links:
dbSNP: rs186669805
NCBI 1000 Genomes Browser:
rs186669805
Molecular consequence:
  • NM_174936.4:c.10G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypercholesterolemia, familial, 1
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000690955Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 25, 2017) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000690955.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the signal peptide domain of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in multiple Japanese individuals with FH (PMID 26374825, 27206942) but also reported to be a common polymorphism in Japan (PMID 14727156, 27206942). This variant has been identified in 7/1727 East Asian chromosomes in the Exome Aggregation Consortium (ExAC) general population database.

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

Last Updated: May 16, 2025