U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.1066G>A (p.Asp356Asn) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 18, 2025
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:
RCV003387819.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1066G>A (p.Asp356Asn)]

NM_000527.5(LDLR):c.1066G>A (p.Asp356Asn)

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.1066G>A (p.Asp356Asn)
HGVS:
  • NC_000019.10:g.11111519G>A
  • NG_009060.1:g.27139G>A
  • NM_000527.5:c.1066G>AMANE SELECT
  • NM_001195798.2:c.1066G>A
  • NM_001195799.2:c.943G>A
  • NM_001195800.2:c.562G>A
  • NM_001195803.2:c.685G>A
  • NP_000518.1:p.Asp356Asn
  • NP_000518.1:p.Asp356Asn
  • NP_001182727.1:p.Asp356Asn
  • NP_001182728.1:p.Asp315Asn
  • NP_001182729.1:p.Asp188Asn
  • NP_001182732.1:p.Asp229Asn
  • LRG_274t1:c.1066G>A
  • LRG_274:g.27139G>A
  • LRG_274p1:p.Asp356Asn
  • NC_000019.9:g.11222195G>A
  • NM_000527.4:c.1066G>A
  • c.1066G>A
Protein change:
D188N
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000157; dbSNP: rs767767730
NCBI 1000 Genomes Browser:
rs767767730
Molecular consequence:
  • NM_000527.5:c.1066G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1066G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.943G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.562G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.685G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004099697Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Apr 18, 2025) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutation scanning by meltMADGE: validations using BRCA1 and LDLR, and demonstration of the potential to identify severe, moderate, silent, rare, and paucimorphic mutations in the general population.

Alharbi KK, Aldahmesh MA, Spanakis E, Haddad L, Whittall RA, Chen XH, Rassoulian H, Smith MJ, Sillibourne J, Ball NJ, Graham NJ, Briggs PJ, Simpson IA, Phillips DI, Lawlor DA, Ye S, Humphries SE, Cooper C, Smith GD, Ebrahim S, Eccles DM, Day IN.

Genome Res. 2005 Jul;15(7):967-77.

PubMed [citation]
PMID:
15998910
PMCID:
PMC1172041

Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database.

Leigh SE, Foster AH, Whittall RA, Hubbart CS, Humphries SE.

Ann Hum Genet. 2008 Jul;72(Pt 4):485-98. doi: 10.1111/j.1469-1809.2008.00436.x. Epub 2008 Mar 5.

PubMed [citation]
PMID:
18325082
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004099697.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: LDLR c.1066G>A (p.Asp356Asn) results in a conservative amino acid change located in the EGF-like calcium-binding domain (IPR001881) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251248 control chromosomes. c.1066G>A has been reported in the literature in individuals affected with Familial Hypercholesterolemia (e.g. Alharbi_2005, Leigh_2008, Taylor_2009, Chmara_2010, Bertolini_2020), however without strong evidence for causality (e.g., co-segregation data). These reports therefore do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. Additionally, other missense variants affecting the same codon, including p.Asp356His and p.Asp356Tyr, have been reported in multiple patients with familial hypercholesterolemia and are classified as pathogenic/likely pathogenic, suggesting that disruption of this residue is clinically significant. The following publications have been ascertained in the context of this evaluation (PMID: 15998910, 32977124, 20145306, 18325082, 19843101). ClinVar contains an entry for this variant (Variation ID: 251643). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Sep 27, 2025