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NM_000527.5(LDLR):c.1124A>G (p.Tyr375Cys) AND Hypercholesterolemia, familial, 1

Germline classification:
Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:
Sep 5, 2019
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000237921.9

Allele description [Variation Report for NM_000527.5(LDLR):c.1124A>G (p.Tyr375Cys)]

NM_000527.5(LDLR):c.1124A>G (p.Tyr375Cys)

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.1124A>G (p.Tyr375Cys)
HGVS:
  • NC_000019.10:g.11111577A>G
  • NG_009060.1:g.27197A>G
  • NM_000527.5:c.1124A>GMANE SELECT
  • NM_001195798.2:c.1124A>G
  • NM_001195799.2:c.1001A>G
  • NM_001195800.2:c.620A>G
  • NM_001195803.2:c.743A>G
  • NP_000518.1:p.Tyr375Cys
  • NP_000518.1:p.Tyr375Cys
  • NP_001182727.1:p.Tyr375Cys
  • NP_001182728.1:p.Tyr334Cys
  • NP_001182729.1:p.Tyr207Cys
  • NP_001182732.1:p.Tyr248Cys
  • LRG_274t1:c.1124A>G
  • LRG_274:g.27197A>G
  • LRG_274p1:p.Tyr375Cys
  • NC_000019.9:g.11222253A>G
  • NM_000527.4:c.1124A>G
  • c.1124A>G
Protein change:
Y207C
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000528; dbSNP: rs879254800
NCBI 1000 Genomes Browser:
rs879254800
Molecular consequence:
  • NM_000527.5:c.1124A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1124A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1001A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.620A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.743A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
6

Condition(s)

Name:
Hypercholesterolemia, familial, 1
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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000295235LDLR-LOVD, British Heart Foundation
criteria provided, single submitter

(ACGS Guidelines, 2013)
Likely pathogenic
(Mar 25, 2016)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000503302Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Dec 16, 2016)
germlineclinical testing

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

SCV000583792U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 30, 2017)
germlineclinical testing

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

SCV000607561Fundacion Hipercolesterolemia Familiar - SAFEHEART
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Mar 1, 2016)
germlineresearch

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

SCV000894173Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Oct 31, 2018)
unknownclinical testing

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

SCV001433510Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Sep 5, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyes266not provided2603not providedclinical testing, literature only
not providedgermlineunknownnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

García-García AB, Real JT, Puig O, Cebolla E, Marín-García P, Martínez Ferrandis JI, García-Sogo M, Civera M, Ascaso JF, Carmena R, Armengod ME, Chaves FJ.

Hum Mutat. 2001 Nov;18(5):458-9.

PubMed [citation]
PMID:
11668640

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
See all PubMed Citations (4)
PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]
PMCID:
PMC4544753
PMID:
25741868
DOI:
10.1038/gim.2015.30

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295235.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (3)
2not provided1not providednot providedliterature only PubMed (3)
3not provided1not providednot providedliterature only PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided
2germlineyes1not providednot provided1not providednot providednot provided
3germlineyes1not providednot provided1not providednot providednot provided

From Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503302.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)

Description

subjects mutated among 2600 FH index cases screened = 3 , family members = 4 with co-segregation / previously described in association with FH / Software predictions: Damaging

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes2600not providednot provided3not providednot providednot provided

From U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583792.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided20not providednot providedclinical testing PubMed (1)

Description

Dutch Lipid Clinic Scoring : Probable FH

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided20not provided6not provided

From Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607561.1

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

Description

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

From Fulgent Genetics, Fulgent Genetics, SCV000894173.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV001433510.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024