NM_000527.5(LDLR):c.1297G>C (p.Asp433His) AND Familial hypercholesterolemia 1

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 25, 2016)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000003930.9

Allele description [Variation Report for NM_000527.5(LDLR):c.1297G>C (p.Asp433His)]

NM_000527.5(LDLR):c.1297G>C (p.Asp433His)

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.1297G>C (p.Asp433His)
Other names:
D412H; FH Osaka 3
HGVS:
  • NC_000019.10:g.11113388G>C
  • NG_009060.1:g.29008G>C
  • NM_000527.4:c.1297G>C
  • NM_000527.5:c.1297G>CMANE SELECT
  • NM_001195798.2:c.1297G>C
  • NM_001195799.2:c.1174G>C
  • NM_001195800.2:c.793G>C
  • NM_001195803.2:c.916G>C
  • NP_000518.1:p.Asp433His
  • NP_000518.1:p.Asp433His
  • NP_001182727.1:p.Asp433His
  • NP_001182728.1:p.Asp392His
  • NP_001182729.1:p.Asp265His
  • NP_001182732.1:p.Asp306His
  • LRG_274t1:c.1297G>C
  • LRG_274:g.29008G>C
  • NC_000019.9:g.11224064G>C
  • P01130:p.Asp433His
  • c.1297G>C
Protein change:
D265H; ASP412HIS
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001390; UniProtKB: P01130#VAR_005385; OMIM: 606945.0050; dbSNP: rs121908036
NCBI 1000 Genomes Browser:
rs121908036
Molecular consequence:
  • NM_000527.4:c.1297G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000527.5:c.1297G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1297G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1174G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.793G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.916G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial hypercholesterolemia 1 (FHCL1)
Synonyms:
LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000024095OMIMno assertion criteria providedPathogenic
(Nov 15, 1992)
germlineliterature only

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

SCV000295350LDLR-LOVD, British Heart Foundationcriteria provided, single submitter
Likely pathogenic
(Mar 25, 2016)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000606385Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrumno assertion criteria providedPathogenicgermlineresearch

SCV000607582Fundacion Hipercolesterolemia Familiar - SAFEHEARTcriteria provided, single submitter
Pathogenic
(Mar 1, 2016)
germlineresearch

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot provided2not providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedresearch
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A point mutation of low-density-lipoprotein receptor causing rapid degradation of the receptor.

Miyake Y, Tajima S, Funahashi T, Yamamura T, Yamamoto A.

Eur J Biochem. 1992 Nov 15;210(1):1-7.

PubMed [citation]
PMID:
1446662

Molecular characterization of familial hypercholesterolemia in Spain: identification of 39 novel and 77 recurrent mutations in LDLR.

Mozas P, Castillo S, Tejedor D, Reyes G, Alonso R, Franco M, Saenz P, Fuentes F, Almagro F, Mata P, PocovĂ­ M.

Hum Mutat. 2004 Aug;24(2):187.

PubMed [citation]
PMID:
15241806
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000024095.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a Japanese patient with homozygous familial hypercholesterolemia (FHCL1; 143890), Miyake et al. (1992) identified a G-to-C transversion in exon 9 which was predicted to change asp412 to his. The amino acid change occurred in the epidermal growth factor precursor homology domain of the LDL receptor. Both in the fibroblasts of the patient and in transfected COS-1 cells, the mutant protein showed impaired processing and rapid degradation. Members of the family carrying the mutant gene in heterozygous state showed higher serum cholesterol levels than the others; however, cholesterol levels were also influenced by the apolipoprotein E phenotype. The mutant LDLR reported by Miyake et al. (1992) is designated here FH Osaka-3.

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

From LDLR-LOVD, British Heart Foundation, SCV000295350.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (2)
2not provided1not providednot providedliterature only PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided
2germlineyes1not providednot provided1not providednot providednot provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum, SCV000606385.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607582.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)
2not providednot providednot providednot providedresearch PubMed (2)

Description

"Hmz patients' fibroblasts, 125I-LDL assays, just binding"
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided
2germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 29, 2020

Support Center