NM_000527.5(LDLR):c.1247G>T (p.Arg416Leu) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Mar 23, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000237152.7

Allele description [Variation Report for NM_000527.5(LDLR):c.1247G>T (p.Arg416Leu)]

NM_000527.5(LDLR):c.1247G>T (p.Arg416Leu)

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.1247G>T (p.Arg416Leu)

HGVS:

NC_000019.10:g.11113338G>T
NG_009060.1:g.28958G>T
NM_000527.5:c.1247G>TMANE SELECT
NM_001195798.2:c.1247G>T
NM_001195799.2:c.1124G>T
NM_001195800.2:c.743G>T
NM_001195803.2:c.866G>T
NP_000518.1:p.Arg416Leu
NP_000518.1:p.Arg416Leu
NP_001182727.1:p.Arg416Leu
NP_001182728.1:p.Arg375Leu
NP_001182729.1:p.Arg248Leu
NP_001182732.1:p.Arg289Leu
LRG_274t1:c.1247G>T
LRG_274:g.28958G>T
LRG_274p1:p.Arg416Leu
NC_000019.9:g.11224014G>T
NM_000527.4:c.1247G>T
c.1247G>T

Protein change:

R248L

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000181; dbSNP: rs773658037

NCBI 1000 Genomes Browser:

rs773658037

Molecular consequence:

NM_000527.5:c.1247G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1247G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1124G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.743G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.866G>T - 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

Recent activity

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ureide permease 2 [Arabidopsis thaliana]
ureide permease 2 [Arabidopsis thaliana]
gi|145359873|ref|NP_178451.2|

Protein
ALDH1B1 [Canis lupus dingo]
ALDH1B1 [Canis lupus dingo]
Gene ID:112650106

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295327	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000606375	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research
SCV002022668	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295327

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Likely pathogenic
(Mar 25, 2016)

germline

literature only

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

Citation Link,

SCV000606375

Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum

no assertion criteria provided

Pathogenic

germline

research

SCV002022668

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 23, 2020)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, research

Citations

PubMed

Detection of mutations and large rearrangements of the low-density lipoprotein receptor gene in Taiwanese patients with familial hypercholesterolemia.

Chiou KR, Charng MJ.

Am J Cardiol. 2010 Jun 15;105(12):1752-8. doi: 10.1016/j.amjcard.2010.01.356. Epub 2010 May 4.

PubMed [citation]

PMID:: 20538126

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295327.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606375.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002022668.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 16, 2024

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