NM_000527.5(LDLR):c.1906G>A (p.Gly636Ser) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 5, 2016
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:: RCV002411105.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1906G>A (p.Gly636Ser)]

NM_000527.5(LDLR):c.1906G>A (p.Gly636Ser)

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.1906G>A (p.Gly636Ser)

Other names:

NM_000527.5(LDLR):c.1906G>A; p.Gly636Ser

HGVS:

NC_000019.10:g.11120152G>A
NG_009060.1:g.35772G>A
NM_000527.5:c.1906G>AMANE SELECT
NM_001195798.2:c.1906G>A
NM_001195799.2:c.1783G>A
NM_001195800.2:c.1402G>A
NM_001195803.2:c.1525G>A
NP_000518.1:p.Gly636Ser
NP_001182727.1:p.Gly636Ser
NP_001182728.1:p.Gly595Ser
NP_001182729.1:p.Gly468Ser
NP_001182732.1:p.Gly509Ser
LRG_274t1:c.1906G>A
LRG_274:g.35772G>A
NC_000019.9:g.11230828G>A
NM_000527.4:c.1906G>A
c.1906G>A

Protein change:

G468S

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000905; dbSNP: rs764550980

NCBI 1000 Genomes Browser:

rs764550980

Molecular consequence:

NM_000527.5:c.1906G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1906G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1783G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1402G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1525G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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Transcriptional factor B3 family protein [Arabidopsis thaliana]
Transcriptional factor B3 family protein [Arabidopsis thaliana]
gi|30689117|ref|NP_194896.2|

Protein
GPRIN3 AND (alive[prop]) (562)
Gene
L1TD1 AND (alive[prop]) (186)
Gene
Gm29788 predicted gene, 29788 [Mus musculus]
Gm29788 predicted gene, 29788 [Mus musculus]
Gene ID:101056148

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002722022	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (May 5, 2016)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15823288, 16542394, 20809525, 24671153 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002722022

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(May 5, 2016)

germline

clinical testing

PubMed (4)
[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

The relationship of molecular genetic to clinical diagnosis of familial hypercholesterolemia in a Danish population.

Damgaard D, Larsen ML, Nissen PH, Jensen JM, Jensen HK, Soerensen VR, Jensen LG, Faergeman O.

Atherosclerosis. 2005 May;180(1):155-60. Epub 2005 Jan 12.

PubMed [citation]

PMID:: 15823288

Molecular genetic analysis of 1053 Danish individuals with clinical signs of familial hypercholesterolemia.

Brusgaard K, Jordan P, Hansen H, Hansen AB, Hørder M.

Clin Genet. 2006 Mar;69(3):277-83.

PubMed [citation]

PMID:: 16542394

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002722022.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The p.G636S variant (also known as c.1906G>A), located in coding exon 13 of the LDLR gene, results from a G to A substitution at nucleotide position 1906. The glycine at codon 636 is replaced by serine, an amino acid with similar properties, and is located in the EGF precursor like domain. This alteration was reported in two individuals meeting clinical criteria for familial hypercholesterolemia (Damgaard et al. Atherosclerosis 2005;180(1):155-60; Brusgaard et al. Clin. Genet. 2006;69(3):277-83). Other alterations at the same amino acid position (also described as p.G615 in the literature), have been reported: p.G636D (c.1907G>A) and p.G636V (c.1907G>T) (Marduel et al. Hum. Mutat. 2010:31(11):E1811-24; Wang et al. PLoS ONE 2014;9(3):e92703). Based on data from ExAC, the A allele has an overall frequency of <0.01% (1/106207). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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: May 7, 2024

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