NM_000527.5(LDLR):c.1374_1375del (p.Arg458fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 25, 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:: RCV000237537.10

Allele description [Variation Report for NM_000527.5(LDLR):c.1374_1375del (p.Arg458fs)]

NM_000527.5(LDLR):c.1374_1375del (p.Arg458fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1374_1375del (p.Arg458fs)

Other names:

FH Ancona

HGVS:

NC_000019.10:g.11113548AG[1]
NG_009060.1:g.29168AG[1]
NG_009060.1:g.29170_29171del
NM_000527.5:c.1374_1375delMANE SELECT
NM_001195798.2:c.1374_1375del
NM_001195799.2:c.1251_1252del
NM_001195800.2:c.870_871del
NM_001195803.2:c.993_994del
NP_000518.1:p.Arg458fs
NP_001182727.1:p.Arg458fs
NP_001182728.1:p.Arg417fs
NP_001182729.1:p.Arg290fs
NP_001182732.1:p.Arg331fs
LRG_274:g.29168AG[1]
NC_000019.9:g.11224224AG[1]
NG_009060.1:g.29170_29171del
NM_000527.4:c.1374_1375del
c.1374_1375del

Protein change:

R290fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000545; dbSNP: rs879254884

NCBI 1000 Genomes Browser:

rs879254884

Molecular consequence:

NM_000527.5:c.1374_1375del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.1374_1375del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.1251_1252del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.870_871del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.993_994del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295401	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10978268, 17347910 Citation Link,
SCV000322947	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	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

SCV000295401

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Pathogenic
(Mar 25, 2016)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000322947

Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge

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	yes	2	not provided	not provided	2	not provided	research, literature only

Citations

PubMed

Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype.

Bertolini S, Cantafora A, Averna M, Cortese C, Motti C, Martini S, Pes G, Postiglione A, Stefanutti C, Blotta I, Pisciotta L, Rolleri M, Langheim S, Ghisellini M, Rabbone I, Calandra S.

Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):E41-52.

PubMed [citation]

PMID:: 10978268

Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 defect by means of DNA analysis of LDL-receptor gene mutations.

Widhalm K, Dirisamer A, Lindemayr A, Kostner G.

J Inherit Metab Dis. 2007 Apr;30(2):239-47. Epub 2007 Mar 8.

PubMed [citation]

PMID:: 17347910

See all PubMed Citations (3)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295401.2

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

From Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000322947.1

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

Description

0/184 non-FH alleles

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

Last Updated: Oct 26, 2024

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