U.S. flag

An official website of the United States government

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002722022Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(May 5, 2016) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024