NM_000527.5(LDLR):c.1004G>T (p.Gly335Val) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 14, 2017
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:: RCV002401931.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1004G>T (p.Gly335Val)]

NM_000527.5(LDLR):c.1004G>T (p.Gly335Val)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1004G>T (p.Gly335Val)

Other names:

NM_000527.5(LDLR):c.1004G>T; p.Gly335Val

HGVS:

NC_000019.10:g.11110715G>T
NG_009060.1:g.26335G>T
NM_000527.5:c.1004G>TMANE SELECT
NM_001195798.2:c.1004G>T
NM_001195799.2:c.881G>T
NM_001195800.2:c.500G>T
NM_001195803.2:c.623G>T
NP_000518.1:p.Gly335Val
NP_000518.1:p.Gly335Val
NP_001182727.1:p.Gly335Val
NP_001182728.1:p.Gly294Val
NP_001182729.1:p.Gly167Val
NP_001182732.1:p.Gly208Val
LRG_274t1:c.1004G>T
LRG_274:g.26335G>T
LRG_274p1:p.Gly335Val
NC_000019.9:g.11221391G>T
NM_000527.4:c.1004G>T
c.1004G>T

Protein change:

G167V

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000335; dbSNP: rs869320650

NCBI 1000 Genomes Browser:

rs869320650

Molecular consequence:

NM_000527.5:c.1004G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1004G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.881G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.500G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.623G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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pancreatic polypeptide prohormone precursor [Mus musculus]
pancreatic polypeptide prohormone precursor [Mus musculus]
gi|6679453|ref|NP_032944.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002710223	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Sep 14, 2017)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 10735632, 11668627, 1301956, 15556094, 19318025, 21382890, 22390909, 23375686, 27578127, 28502510 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002710223

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Sep 14, 2017)

germline

clinical testing

PubMed (10)
[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

Molecular genetic testing for familial hypercholesterolemia: spectrum of LDL receptor gene mutations in The Netherlands.

Lombardi MP, Redeker EJ, Defesche JC, Kamerling SW, Trip MD, Mannens MM, Havekes LM, Kastelein JJ.

Clin Genet. 2000 Feb;57(2):116-24.

PubMed [citation]

PMID:: 10735632

Low density lipoprotein receptor (LDLR) gene mutations in Canadian subjects with familial hypercholesterolemia, but not of French descent.

Wang J, Huff E, Janecka L, Hegele RA.

Hum Mutat. 2001 Oct;18(4):359.

PubMed [citation]

PMID:: 11668627

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV002710223.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The p.G335V variant (also known as c.1004G>T), located in coding exon 7 of the LDLR gene, results from a G to T substitution at nucleotide position 1004. The glycine at codon 335 is replaced by valine, an amino acid with dissimilar properties. This alteration, also known as G314V, has been reported in familial hypercholesterolemia (FH) cohorts in the Netherlands and Spain (Lombardi MP et al. Clin. Genet., 2000 Feb;57:116-24; van der Graaf A et al. Circulation, 2011 Mar;123:1167-73; Alonso R et al. Clin. Biochem., 2009 Jun;42:899-903; Huijgen R et al. Eur. Heart J., 2012 Sep;33:2325-30). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Another alteration affecting the same amino acid, G335S, has been described in a number of FH cohorts (Hobbs HH et al. Hum. Mutat., 1992;1:445-66; Wang J et al. Hum. Mutat., 2001 Oct;18:359; Laurie AD et al. Atheroscler Suppl, 2004 Dec;5:13-5; Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8; Rabacchi C et al. J Clin Lipidol Apr;10:944-952.e1; Bañares VG et al. J Clin Lipidol Feb;11:524-531). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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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