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NM_000527.5(LDLR):c.1130G>C (p.Cys377Ser) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 15, 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:
RCV002321917.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1130G>C (p.Cys377Ser)]

NM_000527.5(LDLR):c.1130G>C (p.Cys377Ser)

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.1130G>C (p.Cys377Ser)
HGVS:
  • NC_000019.10:g.11111583G>C
  • NG_009060.1:g.27203G>C
  • NM_000527.5:c.1130G>CMANE SELECT
  • NM_001195798.2:c.1130G>C
  • NM_001195799.2:c.1007G>C
  • NM_001195800.2:c.626G>C
  • NM_001195803.2:c.749G>C
  • NP_000518.1:p.Cys377Ser
  • NP_001182727.1:p.Cys377Ser
  • NP_001182728.1:p.Cys336Ser
  • NP_001182729.1:p.Cys209Ser
  • NP_001182732.1:p.Cys250Ser
  • LRG_274t1:c.1130G>C
  • LRG_274:g.27203G>C
  • NC_000019.9:g.11222259G>C
  • NM_000527.4:c.1130G>C
  • c.1130G>C
Protein change:
C209S
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001363; dbSNP: rs879254801
NCBI 1000 Genomes Browser:
rs879254801
Molecular consequence:
  • NM_000527.5:c.1130G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1130G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1007G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.626G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.749G>C - 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
SCV002610571Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 15, 2017) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

Bertolini S, Pisciotta L, Rabacchi C, Cefalù AB, Noto D, Fasano T, Signori A, Fresa R, Averna M, Calandra S.

Atherosclerosis. 2013 Apr;227(2):342-8. doi: 10.1016/j.atherosclerosis.2013.01.007. Epub 2013 Jan 19.

PubMed [citation]
PMID:
23375686

Details of each submission

From Ambry Genetics, SCV002610571.2

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

Description

The p.C377S variant (also known as c.1130G>C), located in coding exon 8 of the LDLR gene, results from a G to C substitution at nucleotide position 1130. The cysteine at codon 377 is replaced by serine, an amino acid with dissimilar properties, and is located in the EGF-like B domain. This alteration has been reported in a familial hypercholesterolemia (FH) cohort (Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8). In addition, other alterations involving the same amino acid position, p.C377Y (c.1130G>A), p.C377G (c.1129T>G) and p.C377F (c.1130G>T) have been reported in individuals with FH (Ekström U et al. Eur. J. Clin. Invest. 1998;28:740-7; Romano M et al, J. Lipid Res. 2011; 52:2095-100; Wu WF et al. PLoS ONE 2014; 9:e94697). Based on internal structural assessment, this alteration results in loss of a disulfide motif in EGF domain B; alterations which affect this disulfide are well-established pathogenic alterations. 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: May 1, 2024