NM_174936.4(PCSK9):c.158C>G (p.Ala53Gly) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 29, 2022
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:: RCV002404323.2

Allele description [Variation Report for NM_174936.4(PCSK9):c.158C>G (p.Ala53Gly)]

NM_174936.4(PCSK9):c.158C>G (p.Ala53Gly)

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.158C>G (p.Ala53Gly)

HGVS:

NC_000001.11:g.55039995C>G
NG_009061.1:g.5449C>G
NM_174936.4:c.158C>GMANE SELECT
NP_777596.2:p.Ala53Gly
NP_777596.2:p.Ala53Gly
LRG_275t1:c.158C>G
LRG_275:g.5449C>G
LRG_275p1:p.Ala53Gly
NC_000001.10:g.55505668C>G
NM_174936.3:c.158C>G

Protein change:

A53G

Links:

dbSNP: rs11583680

NCBI 1000 Genomes Browser:

rs11583680

Molecular consequence:

NM_174936.4:c.158C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002708361	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27919364, 32719484 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002708361

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 29, 2022)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Double-heterozygous autosomal dominant hypercholesterolemia: Clinical characterization of an underreported disease.

Sjouke B, Defesche JC, Hartgers ML, Wiegman A, Roeters van Lennep JE, Kastelein JJ, Hovingh GK.

J Clin Lipidol. 2016 Nov-Dec;10(6):1462-1469. doi: 10.1016/j.jacl.2016.09.003. Epub 2016 Sep 13.

PubMed [citation]

PMID:: 27919364

Population genetic screening efficiently identifies carriers of autosomal dominant diseases.

Grzymski JJ, Elhanan G, Morales Rosado JA, Smith E, Schlauch KA, Read R, Rowan C, Slotnick N, Dabe S, Metcalf WJ, Lipp B, Reed H, Sharma L, Levin E, Kao J, Rashkin M, Bowes J, Dunaway K, Slonim A, Washington N, Ferber M, Bolze A, et al.

Nat Med. 2020 Aug;26(8):1235-1239. doi: 10.1038/s41591-020-0982-5. Epub 2020 Jul 27.

PubMed [citation]

PMID:: 32719484

Details of each submission

From Ambry Genetics, SCV002708361.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.A53G variant (also known as c.158C>G), located in coding exon 1 of the PCSK9 gene, results from a C to G substitution at nucleotide position 158. The alanine at codon 53 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a familial hypercholesterolemia (FH) cohort; however, an additional alteration was detected in an associated gene (Sjouke B et al. J Clin Lipidol Sep;10:1462-1469). Additionally, this alteration was detected in a cohort of 29,906 healthy individuals who underwent multigene panel testing (Grzymski JJ et al. Nat Med, 2020 08;26:1235-1239). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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