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NM_174936.4(PCSK9):c.2023G>A (p.Val675Ile) AND Familial hypercholesterolemia

Germline classification:
Likely benign (1 submission)
Last evaluated:
May 16, 2018
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:
RCV000775303.3

Allele description [Variation Report for NM_174936.4(PCSK9):c.2023G>A (p.Val675Ile)]

NM_174936.4(PCSK9):c.2023G>A (p.Val675Ile)

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.2023G>A (p.Val675Ile)
HGVS:
  • NC_000001.11:g.55063528G>A
  • NG_009061.1:g.28982G>A
  • NM_001407240.1:c.2146G>A
  • NM_001407241.1:c.2065G>A
  • NM_001407242.1:c.2026G>A
  • NM_001407243.1:c.1966G>A
  • NM_001407244.1:c.1849G>A
  • NM_001407245.1:c.1831G>A
  • NM_001407246.1:c.1648G>A
  • NM_001407247.1:c.1522G>A
  • NM_174936.4:c.2023G>AMANE SELECT
  • NP_001394169.1:p.Val716Ile
  • NP_001394170.1:p.Val689Ile
  • NP_001394171.1:p.Val676Ile
  • NP_001394172.1:p.Val656Ile
  • NP_001394173.1:p.Val617Ile
  • NP_001394174.1:p.Val611Ile
  • NP_001394175.1:p.Val550Ile
  • NP_001394176.1:p.Val508Ile
  • NP_777596.2:p.Val675Ile
  • NP_777596.2:p.Val675Ile
  • LRG_275t1:c.2023G>A
  • LRG_275:g.28982G>A
  • LRG_275p1:p.Val675Ile
  • NC_000001.10:g.55529201G>A
  • NM_174936.3:c.2023G>A
  • NR_110451.2:n.1630G>A
  • NR_110451.3:n.2304G>A
  • NR_176318.1:n.2107G>A
  • NR_176319.1:n.2582G>A
  • NR_176320.1:n.2546G>A
  • NR_176321.1:n.2261G>A
  • NR_176322.1:n.2216G>A
  • NR_176323.1:n.2135G>A
  • NR_176324.1:n.2523G>A
Protein change:
V508I
Links:
dbSNP: rs760981278
NCBI 1000 Genomes Browser:
rs760981278
Molecular consequence:
  • NM_001407240.1:c.2146G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407241.1:c.2065G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407242.1:c.2026G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407243.1:c.1966G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407244.1:c.1849G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407245.1:c.1831G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407246.1:c.1648G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001407247.1:c.1522G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_174936.4:c.2023G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hypercholesterolemia
Identifiers:
MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000909562Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely benign
(May 16, 2018) 		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, SCV000909562.1

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

Description

Likely Benign based on current evidence: This missense variant is located in the C-terminal, CM3 domain of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. This variant occurs in more than 10 mammalian species, suggesting that the variant is functionally tolerated. 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 nor has the variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 3/244444 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on available evidence, this variant is classified as Likely Benign.

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

Last Updated: Sep 1, 2024