NM_000527.5(LDLR):c.1735G>T (p.Asp579Tyr) AND Familial hypercholesterolemia 1

Clinical significance:Likely pathogenic (Last evaluated: May 24, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
6 submissions [Details]
Record status:
current
Accession:
RCV000211648.8

Allele description [Variation Report for NM_000527.5(LDLR):c.1735G>T (p.Asp579Tyr)]

NM_000527.5(LDLR):c.1735G>T (p.Asp579Tyr)

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.1735G>T (p.Asp579Tyr)
Other names:
FH Casale Monferrato
HGVS:
  • NC_000019.10:g.11116888G>T
  • NG_009060.1:g.32508G>T
  • NM_000527.4:c.1735G>T
  • NM_000527.5:c.1735G>TMANE SELECT
  • NM_001195798.2:c.1735G>T
  • NM_001195799.2:c.1612G>T
  • NM_001195800.2:c.1231G>T
  • NM_001195803.2:c.1354G>T
  • NP_000518.1:p.Asp579Tyr
  • NP_000518.1:p.Asp579Tyr
  • NP_001182727.1:p.Asp579Tyr
  • NP_001182728.1:p.Asp538Tyr
  • NP_001182729.1:p.Asp411Tyr
  • NP_001182732.1:p.Asp452Tyr
  • LRG_274t1:c.1735G>T
  • LRG_274:g.32508G>T
  • LRG_274p1:p.Asp579Tyr
  • NC_000019.9:g.11227564G>T
  • P01130:p.Asp579Tyr
  • c.1735G>T
  • p.(Asp579Tyr)
Protein change:
D411Y
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000561; UniProtKB: P01130#VAR_062382; dbSNP: rs875989929
NCBI 1000 Genomes Browser:
rs875989929
Molecular consequence:
  • NM_000527.4:c.1735G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000527.5:c.1735G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1735G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1612G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1231G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1354G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000268634Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospitalno assertion criteria providedPathogenic
(Jun 26, 2015)
germlineclinical testing

SCV000295625LDLR-LOVD, British Heart Foundationcriteria provided, single submitter
Likely pathogenic
(Mar 25, 2016)
germlineliterature only

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

Citation Link,

SCV000503402Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foixcriteria provided, single submitter
Likely pathogenic
(Dec 16, 2016)
germlineclinical testing

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

SCV000583874U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lillecriteria provided, single submitter
Likely pathogenic
(Mar 30, 2017)
germlineclinical testing

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

SCV000599389Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorgecriteria provided, single submitter
Likely pathogenic
(Mar 1, 2016)
germline, not applicablecuration, literature only

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

SCV001653650Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico IIcriteria provided, single submitter
Likely pathogenic
(May 24, 2021)
germlineclinical testing

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

Description

ACMG Guidelines: Likely Pathogenic (v)

SCV000583874

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes51not provided2601not providedclinical testing, literature only
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providednot applicablenot applicablenot providednot providednot providednot providednot providedliterature only
Caucasiangermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype.

Bertolini S, Cantafora A, Averna M, Cortese C, Motti C, Martini S, Pes G, Postiglione A, Stefanutti C, Blotta I, Pisciotta L, Rolleri M, Langheim S, Ghisellini M, Rabbone I, Calandra S.

Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):E41-52.

PubMed [citation]
PMID:
10978268

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
See all PubMed Citations (4)

Details of each submission

From Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital, SCV000268634.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences

From LDLR-LOVD, British Heart Foundation, SCV000295625.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not 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, SCV000503402.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

subject mutated among 2600 FH index cases screened = 1 /Other mutation at same codon/Software predictions: Conflicting

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes2600not providednot provided1not providednot providednot provided

From U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583874.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

Dutch Lipid Clinic Scoring : Probable FH

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not provided1not provided

From Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599389.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)
2not providednot providednot providednot providedliterature only PubMed (2)

Description

"Assay Description:Htz patients' fibroblasts, 125I-LDL assays"
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided
2not applicablenot applicablenot providednot providednot providednot providednot providednot providednot provided

From Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II, SCV001653650.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian1not providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 21, 2021

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