NM_000527.5(LDLR):c.2085_2103del (p.Ala697fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 16, 2016
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:: RCV000237124.2

Allele description [Variation Report for NM_000527.5(LDLR):c.2085_2103del (p.Ala697fs)]

NM_000527.5(LDLR):c.2085_2103del (p.Ala697fs)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.2085_2103del (p.Ala697fs)

HGVS:

NC_000019.10:g.11120467_11120485del
NG_009060.1:g.36087_36105del
NM_000527.5:c.2085_2103delMANE SELECT
NM_001195798.2:c.2085_2103del
NM_001195799.2:c.1962_1980del
NM_001195800.2:c.1581_1599del
NM_001195803.2:c.1606+234_1606+252del
NP_000518.1:p.Ala697fs
NP_000518.1:p.Ala697fs
NP_001182727.1:p.Ala697fs
NP_001182728.1:p.Ala656fs
NP_001182729.1:p.Ala529fs
LRG_274t1:c.2085_2103del
LRG_274:g.36087_36105del
LRG_274p1:p.Ala697fs
NC_000019.9:g.11231143_11231161del
NM_000527.4:c.2085_2103del
c.2085_2103del
p.Ala697Cysfs*6

Protein change:

A529fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000458; dbSNP: rs879255133

NCBI 1000 Genomes Browser:

rs879255133

Molecular consequence:

NM_000527.5:c.2085_2103del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.2085_2103del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.1962_1980del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1581_1599del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1606+234_1606+252del - intron variant - [Sequence Ontology: SO:0001627]

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

UK self-care support initiatives for older patients with long-term conditions: a...
UK self-care support initiatives for older patients with long-term conditions: a review - Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews

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
SCV000295861	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000503460	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)	Pathogenic (Dec 16, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000607672	Fundacion Hipercolesterolemia Familiar - SAFEHEART	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295861

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Pathogenic
(Mar 25, 2016)

germline

literature only

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

Citation Link,

SCV000503460

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)

Pathogenic
(Dec 16, 2016)

germline

clinical testing

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

SCV000607672

Fundacion Hipercolesterolemia Familiar - SAFEHEART

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2016)

germline

research

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	unknown	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	yes	2	not provided	not provided	2601	not provided	clinical testing, literature only

Citations

PubMed

Identification of recurrent and novel mutations in the LDL receptor gene in Spanish patients with familial hypercholesterolemia. Mutations in brief no. 135. Online.

Cenarro A, Jensen HK, Casao E, Civeira F, González-Bonillo J, Rodríguez-Rey JC, Gregersen N, Pocoví M.

Hum Mutat. 1998;11(5):413.

PubMed [citation]

PMID:: 10206683

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, SCV000295861.2

#	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 Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503460.1

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

Description

subject mutated among 2600 FH index cases screened = 1

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

From Fundacion Hipercolesterolemia Familiar - SAFEHEART, SCV000607672.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	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: Jun 23, 2024

ClinVar

Relating variation to medicine