U.S. flag

An official website of the United States government

NM_000527.5(LDLR):c.44T>A (p.Leu15His) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 28, 2022
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:
RCV000238308.2

Allele description [Variation Report for NM_000527.5(LDLR):c.44T>A (p.Leu15His)]

NM_000527.5(LDLR):c.44T>A (p.Leu15His)

Genes:
LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]
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.44T>A (p.Leu15His)
Other names:
NM_000527.5(LDLR):c.44T>A; p.Leu15His
HGVS:
  • NC_000019.10:g.11089592T>A
  • NG_009060.1:g.5212T>A
  • NM_000527.5:c.44T>AMANE SELECT
  • NM_001195798.2:c.44T>A
  • NM_001195799.2:c.44T>A
  • NM_001195800.2:c.44T>A
  • NM_001195803.2:c.44T>A
  • NP_000518.1:p.Leu15His
  • NP_001182727.1:p.Leu15His
  • NP_001182728.1:p.Leu15His
  • NP_001182729.1:p.Leu15His
  • NP_001182732.1:p.Leu15His
  • LRG_274:g.5212T>A
  • NC_000019.9:g.11200268T>A
  • NR_163945.1:n.68A>T
  • c.44T>A
Protein change:
L15H
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001736; dbSNP: rs879254390
NCBI 1000 Genomes Browser:
rs879254390
Molecular consequence:
  • NM_000527.5:c.44T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.44T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.44T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.44T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.44T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163945.1:n.68A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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
SCV000294421LDLR-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,

SCV002568022ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Aug 28, 2022) 		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

Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program.

Leren TP, Manshaus T, Skovholt U, Skodje T, Nossen IE, Teie C, Sørensen S, Bakken KS.

Semin Vasc Med. 2004 Feb;4(1):75-85. Review.

PubMed [citation]
PMID:
15199436

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000294421.2

#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, SCV002568022.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5(LDLR):c.44T>A (p.Leu15His) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is met.

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

Last Updated: Aug 5, 2023