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NM_000527.5(LDLR):c.797A>G (p.Asp266Gly) AND Hypercholesterolemia, familial, 1

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Nov 14, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000237457.3

Allele description [Variation Report for NM_000527.5(LDLR):c.797A>G (p.Asp266Gly)]

NM_000527.5(LDLR):c.797A>G (p.Asp266Gly)

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.797A>G (p.Asp266Gly)
Other names:
NM_000527.5(LDLR):c.797A>G; p.Asp266Gly
HGVS:
  • NC_000019.10:g.11106667A>G
  • NG_009060.1:g.22287A>G
  • NM_000527.5:c.797A>GMANE SELECT
  • NM_001195798.2:c.797A>G
  • NM_001195799.2:c.674A>G
  • NM_001195800.2:c.314-725A>G
  • NM_001195803.2:c.416A>G
  • NP_000518.1:p.Asp266Gly
  • NP_001182727.1:p.Asp266Gly
  • NP_001182728.1:p.Asp225Gly
  • NP_001182732.1:p.Asp139Gly
  • LRG_274t1:c.797A>G
  • LRG_274:g.22287A>G
  • NC_000019.9:g.11217343A>G
  • NM_000527.4:c.797A>G
  • c.797A>G
Protein change:
D139G
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000940; dbSNP: rs879254678
NCBI 1000 Genomes Browser:
rs879254678
Molecular consequence:
  • NM_001195800.2:c.314-725A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.797A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.797A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.674A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.416A>G - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000294977LDLR-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,

SCV002568112ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Likely pathogenic
(Nov 14, 2021) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Molecular genetic analysis of familial hypercholesterolemia: spectrum and regional difference of LDL receptor gene mutations in Japanese population.

Yu W, Nohara A, Higashikata T, Lu H, Inazu A, Mabuchi H.

Atherosclerosis. 2002 Dec;165(2):335-42. Erratum in: Atherosclerosis. 2004 Jun;174(2):399-400.

PubMed [citation]
PMID:
12417285

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294977.2

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

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV002568112.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5(LDLR): c.797A>G (p.Asp266Gly) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes PM5_Strong, PM2, PP3, PP4 and PS4_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). PM5_Strong - 4 other missense variants in the same codon: - NM_000527.5(LDLR): c.796G>T (p.Asp266Asn) (ClinVar ID 226334) - Pathogenic by these guidelines, - NM_000527.5(LDLR): c.797A>T (p.Asp266Val) (ClinVar ID 251458) - Likely pathogenic by these guidelines, - NM_000527.5(LDLR): c.796A>T (p.Asp266Tyr) (ClinVar ID 251456) – Pathogenic by these guidelines, - NM_000527.5(LDLR):c.798T>A (p.Asp266Glu) - (ClinVar ID 161287) - Pathogenic by these guidelines. There are 3 variants in the same codon classified as Pathogenic by these guidelines; PM2 - This variant is absent from gnomAD (gnomAD v2.1.1); PP3 - REVEL = 0.98; PP4 - Identified in 2 unrelated index cases fulfilling Simon-Broome criteria (published in PMID: 32331935); PS4_Supporting - Variant meets PM2. Identified in 2 unrelated index cases fulfilling Simon-Broome criteria (published in PMID: 32331935);

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

Last Updated: Feb 25, 2025