NM_174936.4(PCSK9):c.100G>A (p.Glu34Lys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 27, 2023
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:: RCV003226344.1

Allele description [Variation Report for NM_174936.4(PCSK9):c.100G>A (p.Glu34Lys)]

NM_174936.4(PCSK9):c.100G>A (p.Glu34Lys)

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.100G>A (p.Glu34Lys)

HGVS:

NC_000001.11:g.55039937G>A
NG_009061.1:g.5391G>A
NM_174936.4:c.100G>AMANE SELECT
NP_777596.2:p.Glu34Lys
NP_777596.2:p.Glu34Lys
LRG_275t1:c.100G>A
LRG_275:g.5391G>A
LRG_275p1:p.Glu34Lys
NC_000001.10:g.55505610G>A
NM_174936.3:c.100G>A

Protein change:

E34K

Links:

dbSNP: rs371030381

NCBI 1000 Genomes Browser:

rs371030381

Molecular consequence:

NM_174936.4:c.100G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003922447	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 27, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003922447

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 27, 2023)

germline

clinical testing

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

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

The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia.

Meshkov A, Ershova A, Kiseleva A, Zotova E, Sotnikova E, Petukhova A, Zharikova A, Malyshev P, Rozhkova T, Blokhina A, Limonova A, Ramensky V, Divashuk M, Khasanova Z, Bukaeva A, Kurilova O, Skirko O, Pokrovskaya M, Mikova V, Snigir E, Akinshina A, Mitrofanov S, et al.

Genes (Basel). 2021 Jan 6;12(1). doi:pii: 66. 10.3390/genes12010066.

PubMed [citation]

PMID:: 33418990
PMCID:: PMC7825309

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003922447.1

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

Description

Variant summary: PCSK9 c.100G>A (p.Glu34Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 184476 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.100G>A has been reported in the literature in at least one individual affected with Familial Hypercholesterolemia without strong evidence for causality (Meshkov_2021). Therefore, this report does not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters have assessed the variant since 2014: all five classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain 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

Last Updated: May 1, 2024

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