NM_174936.4(PCSK9):c.1547G>T (p.Gly516Val) AND Hypercholesterolemia, autosomal dominant, 3

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 30, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001099460.6

Allele description [Variation Report for NM_174936.4(PCSK9):c.1547G>T (p.Gly516Val)]

NM_174936.4(PCSK9):c.1547G>T (p.Gly516Val)

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.1547G>T (p.Gly516Val)

HGVS:

NC_000001.11:g.55059529G>T
NG_009061.1:g.24983G>T
NM_001407240.1:c.1670G>T
NM_001407241.1:c.1589G>T
NM_001407242.1:c.1550G>T
NM_001407243.1:c.1490G>T
NM_001407244.1:c.1373G>T
NM_001407245.1:c.1355G>T
NM_001407246.1:c.1172G>T
NM_174936.4:c.1547G>TMANE SELECT
NP_001394169.1:p.Gly557Val
NP_001394170.1:p.Gly530Val
NP_001394171.1:p.Gly517Val
NP_001394172.1:p.Gly497Val
NP_001394173.1:p.Gly458Val
NP_001394174.1:p.Gly452Val
NP_001394175.1:p.Gly391Val
NP_777596.2:p.Gly516Val
NP_777596.2:p.Gly516Val
LRG_275t1:c.1547G>T
LRG_275:g.24983G>T
LRG_275p1:p.Gly516Val
NC_000001.10:g.55525202G>T
NM_174936.3:c.1547G>T
NR_110451.2:n.1154G>T
NR_110451.3:n.1828G>T
NR_176318.1:n.1521G>T
NR_176319.1:n.2106G>T
NR_176320.1:n.1960G>T
NR_176321.1:n.1785G>T
NR_176322.1:n.1740G>T
NR_176324.1:n.2047G>T

Protein change:

G391V

Links:

Molecular consequence:

NM_001407240.1:c.1670G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407241.1:c.1589G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407242.1:c.1550G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407243.1:c.1490G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407244.1:c.1373G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407245.1:c.1355G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407246.1:c.1172G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_174936.4:c.1547G>T - 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

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Foreword by Ben Goldacre - Testing Treatments
Foreword by Ben Goldacre - Testing Treatments
MULTISPECIES: GDCCVxC domain-containing (seleno)protein [Maricaulis]
MULTISPECIES: GDCCVxC domain-containing (seleno)protein [Maricaulis]
gi|499962314|ref|WP_011643032.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001255916	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002785344	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 30, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001255916

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

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

Citation Link,

SCV002785344

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 30, 2021)

unknown

clinical testing

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France.

Wintjens R, Bozon D, Belabbas K, MBou F, Girardet JP, Tounian P, Jolly M, Boccara F, Cohen A, Karsenty A, Dubern B, Carel JC, Azar-Kolakez A, Feillet F, Labarthe F, Gorsky AM, Horovitz A, Tamarindi C, Kieffer P, Lienhardt A, Lascols O, Di Filippo M, et al.

J Lipid Res. 2016 Mar;57(3):482-91. doi: 10.1194/jlr.P055699. Epub 2016 Jan 22.

PubMed [citation]

PMID:: 26802169
PMCID:: PMC4766997

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 Illumina Laboratory Services, Illumina, SCV001255916.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002785344.1

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

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

Last Updated: Sep 1, 2024

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