NM_000527.5(LDLR):c.1796T>C (p.Leu599Ser) AND Hypercholesterolemia, familial, 1

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Jan 22, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000237846.7

Allele description [Variation Report for NM_000527.5(LDLR):c.1796T>C (p.Leu599Ser)]

NM_000527.5(LDLR):c.1796T>C (p.Leu599Ser)

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.1796T>C (p.Leu599Ser)

Other names:

FH London-5

HGVS:

NC_000019.10:g.11116949T>C
NG_009060.1:g.32569T>C
NM_000527.5:c.1796T>CMANE SELECT
NM_001195798.2:c.1796T>C
NM_001195799.2:c.1673T>C
NM_001195800.2:c.1292T>C
NM_001195803.2:c.1415T>C
NP_000518.1:p.Leu599Ser
NP_000518.1:p.Leu599Ser
NP_001182727.1:p.Leu599Ser
NP_001182728.1:p.Leu558Ser
NP_001182729.1:p.Leu431Ser
NP_001182732.1:p.Leu472Ser
LRG_274t1:c.1796T>C
LRG_274:g.32569T>C
LRG_274p1:p.Leu599Ser
NC_000019.9:g.11227625T>C
NM_000527.4:c.1796T>C
P01130:p.Leu599Ser
c.1796T>C

Protein change:

L431S

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001523; UniProtKB: P01130#VAR_005404; dbSNP: rs879255025

NCBI 1000 Genomes Browser:

rs879255025

Molecular consequence:

NM_000527.5:c.1796T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1796T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1673T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1292T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1415T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295662	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Uncertain significance (Mar 25, 2016)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 12436241, 1301956, 19318025 Citation Link,
SCV000503415	Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 16, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000583884	U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000607641	Fundacion Hipercolesterolemia Familiar - SAFEHEART	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 1, 2016)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 1301956
SCV001432596	Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 22, 2019)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 31345425

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	13	3	not provided	2605	not provided	clinical testing, literature only, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.

Amsellem S, Briffaut D, Carrié A, Rabès JP, Girardet JP, Fredenrich A, Moulin P, Krempf M, Reznik Y, Vialettes B, de Gennes JL, Brukert E, Benlian P.

Hum Genet. 2002 Dec;111(6):501-10. Epub 2002 Sep 13.

PubMed [citation]

PMID:: 12436241

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P.

Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

PubMed [citation]

PMID:: 19318025

See all PubMed Citations (5)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295662.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (3)
2	not provided	1	not provided	not provided	literature only	PubMed (3)
3	not provided	1	not provided	not provided	literature only	PubMed (3)

#	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
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
3	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503415.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (1)

Description

subjects mutated among 2600 FH index cases screened = 5 , family member = 1 with co-segregation / FH-London-5, 5 to 15% LDLR Activity/Software predictions: Conflicting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	2600	not provided	not provided		5	not provided	not provided	not provided

From U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, SCV000583884.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (1)

Description

Dutch Lipid Clinic Scoring : Definite FH

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	3	not provided

From Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607641.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)
2	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

"Comp htz (with unknown allele that generates 4,5kb mRNA) patient's fibroblasts, 125I-LDL assays"

PubMed [ID: 1301956]

#	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
2	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia, SCV001432596.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (2)
2	not provided	1	not provided	not provided	research	PubMed (2)

#	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
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine