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NM_000527.5(LDLR):c.1727A>C (p.Tyr576Ser) AND Hypercholesterolemia, familial, 1

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Mar 25, 2016
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:
RCV000237268.9

Allele description [Variation Report for NM_000527.5(LDLR):c.1727A>C (p.Tyr576Ser)]

NM_000527.5(LDLR):c.1727A>C (p.Tyr576Ser)

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.1727A>C (p.Tyr576Ser)
HGVS:
  • NC_000019.10:g.11116880A>C
  • NG_009060.1:g.32500A>C
  • NM_000527.5:c.1727A>CMANE SELECT
  • NM_001195798.2:c.1727A>C
  • NM_001195799.2:c.1604A>C
  • NM_001195800.2:c.1223A>C
  • NM_001195803.2:c.1346A>C
  • NP_000518.1:p.Tyr576Ser
  • NP_001182727.1:p.Tyr576Ser
  • NP_001182728.1:p.Tyr535Ser
  • NP_001182729.1:p.Tyr408Ser
  • NP_001182732.1:p.Tyr449Ser
  • LRG_274:g.32500A>C
  • NC_000019.9:g.11227556A>C
  • c.1727A>C
Protein change:
Y408S
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001152; dbSNP: rs879254999
NCBI 1000 Genomes Browser:
rs879254999
Molecular consequence:
  • NM_000527.5:c.1727A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1727A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1604A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1223A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1346A>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000295615LDLR-LOVD, British Heart Foundation
criteria provided, single submitter

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

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

Citation Link,

SCV004022249deCODE genetics, Amgen
no assertion criteria provided
Likely pathogenic
(Jul 21, 2023)
germlineresearch

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedliterature only
Icelandicgermlineyes11not providednot providednot providednot providedresearch

Citations

PubMed

Molecular spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network., Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]
PMID:
20809525
PMCID:
PMC3152176

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295615.2

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

From deCODE genetics, Amgen, SCV004022249.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Icelandic11not providednot providedresearchnot provided

Description

The variant NM_000527.5:c.1727A>C (chr19:11116880) in LDLR was detected in 7 heterozygotes out of 58K WGS Icelanders (MAF= 0,006%). Following imputation in a set of 166K Icelanders (11 imputed heterozygotes) we observed an association with LDL cholesterol using measurements from 128289 individuals (Effect (SD)= 1.88, P= 1.57e-06) and Non-HDL cholesterol using measurements from 136901 individuals (Effect (SD)= 1.87, P= 1.82e-06). This variant has been reported in ClinVar previously as likely pathogenic. Based on ACMG criteria (PS4, PM1, PP3, PP5) this variant classifies as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided11not providednot providednot provided

Last Updated: Feb 4, 2024