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NM_000527.5(LDLR):c.1103G>A (p.Cys368Tyr) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 13, 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:
RCV002429173.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1103G>A (p.Cys368Tyr)]

NM_000527.5(LDLR):c.1103G>A (p.Cys368Tyr)

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.1103G>A (p.Cys368Tyr)
HGVS:
  • NC_000019.10:g.11111556G>A
  • NG_009060.1:g.27176G>A
  • NM_000527.5:c.1103G>AMANE SELECT
  • NM_001195798.2:c.1103G>A
  • NM_001195799.2:c.980G>A
  • NM_001195800.2:c.599G>A
  • NM_001195803.2:c.722G>A
  • NP_000518.1:p.Cys368Tyr
  • NP_000518.1:p.Cys368Tyr
  • NP_001182727.1:p.Cys368Tyr
  • NP_001182728.1:p.Cys327Tyr
  • NP_001182729.1:p.Cys200Tyr
  • NP_001182732.1:p.Cys241Tyr
  • LRG_274t1:c.1103G>A
  • LRG_274:g.27176G>A
  • LRG_274p1:p.Cys368Tyr
  • NC_000019.9:g.11222232G>A
  • NM_000527.4:c.1103G>A
  • P01130:p.Cys368Tyr
  • c.1103G>A
Protein change:
C200Y
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001357; UniProtKB: P01130#VAR_072844
Molecular consequence:
  • NM_000527.5:c.1103G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1103G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.980G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.599G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.722G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002744397Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 13, 2023) 		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

Screening for new mutations in the LDL receptor gene in seven French familial hypercholesterolemia families by the single strand conformation polymorphism method.

Loux N, Saint-Jore B, Collod G, Dairou F, Benlian P, Truffert J, Dastugue B, Douste-Blazy P, de Gennes JL, Junien C, et al.

Hum Mutat. 1992;1(4):325-32.

PubMed [citation]
PMID:
1301940

The molecular basis of familial hypercholesterolaemia in Turkish patients.

Sözen MM, Whittall R, Oner C, Tokatli A, Kalkanoğlu HS, Dursun A, Coşkun T, Oner R, Humphries SE.

Atherosclerosis. 2005 May;180(1):63-71.

PubMed [citation]
PMID:
15823276
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002744397.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The p.C368Y pathogenic mutation (also known as c.1103G>A), located in coding exon 8 of the LDLR gene, results from a G to A substitution at nucleotide position 1103. The cysteine at codon 368 is replaced by tyrosine, an amino acid with highly dissimilar properties. Pathogenic LDLR mutations that result in the substitution or generation of cysteine residues within the cysteine-rich LDLR class A repeats and EGF-like domains are common in familial hypercholesterolemia (FH) (Villéger L. Hum Mutat. 2002;20(2):81-7). Internal structural analysis indicates this alteration eliminates a disulfide bond critical for the structural integrity of (the) EGF-like 2 domain (Ambry internal data). This variant, which is also known as p.C347Y, has been detected in several individuals with clinically diagnosed hypercholesterolemia (Loux N et al. Hum. Mutat., 1992;1:325-32; Jannes CE et al. Atherosclerosis, 2015 Jan;238:101-7; Vaca G et al. Atherosclerosis, 2011 Oct;218:391-6; Ambry internal data). Another alteration at the same codon, p.C368G (c.1102T>G), has been detected in an individual with clinically diagnosed hypercholesterolemia (Sözen MM et al. Atherosclerosis, 2005 May;180:63-71). In addition, this alteration is predicted to be deleterious by BayesDel in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Jan 13, 2025