NM_174936.4(PCSK9):c.1773C>G (p.His591Gln) AND Cardiovascular phenotype

Germline classification:: Likely benign (1 submission)
Last evaluated:: Jul 20, 2021
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:: RCV002402115.2

Allele description [Variation Report for NM_174936.4(PCSK9):c.1773C>G (p.His591Gln)]

NM_174936.4(PCSK9):c.1773C>G (p.His591Gln)

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.1773C>G (p.His591Gln)

HGVS:

NC_000001.11:g.55061466C>G
NG_009061.1:g.26920C>G
NM_001407240.1:c.1896C>G
NM_001407241.1:c.1815C>G
NM_001407242.1:c.1776C>G
NM_001407243.1:c.1716C>G
NM_001407244.1:c.1599C>G
NM_001407245.1:c.1581C>G
NM_001407246.1:c.1398C>G
NM_001407247.1:c.1272C>G
NM_174936.4:c.1773C>GMANE SELECT
NP_001394169.1:p.His632Gln
NP_001394170.1:p.His605Gln
NP_001394171.1:p.His592Gln
NP_001394172.1:p.His572Gln
NP_001394173.1:p.His533Gln
NP_001394174.1:p.His527Gln
NP_001394175.1:p.His466Gln
NP_001394176.1:p.His424Gln
NP_777596.2:p.His591Gln
NP_777596.2:p.His591Gln
LRG_275t1:c.1773C>G
LRG_275:g.26920C>G
LRG_275p1:p.His591Gln
NC_000001.10:g.55527139C>G
NM_174936.3:c.1773C>G
NR_110451.2:n.1380C>G
NR_110451.3:n.2054C>G
NR_176318.1:n.1857C>G
NR_176319.1:n.2332C>G
NR_176320.1:n.2296C>G
NR_176321.1:n.2011C>G
NR_176322.1:n.1966C>G
NR_176323.1:n.1885C>G
NR_176324.1:n.2273C>G

Protein change:

H424Q

Links:

dbSNP: rs529912877

NCBI 1000 Genomes Browser:

rs529912877

Molecular consequence:

NM_001407240.1:c.1896C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407241.1:c.1815C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407242.1:c.1776C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407243.1:c.1716C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407244.1:c.1599C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407245.1:c.1581C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407246.1:c.1398C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407247.1:c.1272C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_174936.4:c.1773C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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Prunus nitida (0)
BioSample
Cardamine graeca isolate HD569 tRNA-Leu (trnL) gene, intron; chloroplast
Cardamine graeca isolate HD569 tRNA-Leu (trnL) gene, intron; chloroplast
gi|215513823|gb|FJ384296.1|

Nucleotide
homeobox protein Nkx-2.5 isoform 3 [Homo sapiens]
homeobox protein Nkx-2.5 isoform 3 [Homo sapiens]
gi|260898752|ref|NP_001159648.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002711862	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Jul 20, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29259136, 30487145 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002711862

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Jul 20, 2021)

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

Stepwise processing analyses of the single-turnover PCSK9 protease reveal its substrate sequence specificity and link clinical genotype to lipid phenotype.

Chorba JS, Galvan AM, Shokat KM.

J Biol Chem. 2018 Feb 9;293(6):1875-1886. doi: 10.1074/jbc.RA117.000754. Epub 2017 Dec 19. Erratum in: J Biol Chem. 2018 May 4;293(18):6692. doi: 10.1074/jbc.AAC118.003335.

PubMed [citation]

PMID:: 29259136
PMCID:: PMC5808750

High-frequency actionable pathogenic exome variants in an average-risk cohort.

Rego S, Dagan-Rosenfeld O, Zhou W, Sailani MR, Limcaoco P, Colbert E, Avina M, Wheeler J, Craig C, Salins D, Röst HL, Dunn J, McLaughlin T, Steinmetz LM, Bernstein JA, Snyder MP.

Cold Spring Harb Mol Case Stud. 2018 Dec 17;4(6). doi:pii: a003178. 10.1101/mcs.a003178. Print 2018 Dec.

PubMed [citation]

PMID:: 30487145
PMCID:: PMC6318774

Details of each submission

From Ambry Genetics, SCV002711862.2

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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: Sep 29, 2024

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