NM_000527.5(LDLR):c.925_931del (p.Pro309fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic (4 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:: RCV000003927.8

Allele description [Variation Report for NM_000527.5(LDLR):c.925_931del (p.Pro309fs)]

NM_000527.5(LDLR):c.925_931del (p.Pro309fs)

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.925_931del (p.Pro309fs)

Other names:

FH North Karelia

HGVS:

NC_000019.10:g.11107499_11107505del
NG_009060.1:g.23119_23125del
NM_000527.5:c.925_931delMANE SELECT
NM_001195798.2:c.925_931del
NM_001195799.2:c.802_808del
NM_001195800.2:c.421_427del
NM_001195803.2:c.544_550del
NP_000518.1:p.Pro309fs
NP_001182727.1:p.Pro309fs
NP_001182728.1:p.Pro268fs
NP_001182729.1:p.Pro141fs
NP_001182732.1:p.Pro182fs
LRG_274:g.23119_23125del
NC_000019.9:g.11218174_11218180del
NC_000019.9:g.11218175_11218181del
NM_000527.4:c.925_931delCCCATCA
c.925_931del

Protein change:

P141fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001867; OMIM: 606945.0047; dbSNP: rs387906304

NCBI 1000 Genomes Browser:

rs387906304

Molecular consequence:

NM_000527.5:c.925_931del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.925_931del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.802_808del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.421_427del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.544_550del - 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
SCV000024092	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 1997)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 1634609, 9409302
SCV000295060	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 15701167, 15199436, 1634609 Citation Link,
SCV000599351	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2016)	germline, not applicable	curation, literature only	PubMed (2) [See all records that cite these PMIDs] 25741868, 1634609
SCV000606271	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	no assertion criteria provided	Pathogenic	germline	research

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, curation
not provided	germline	yes	3	not provided	not provided	3	not provided	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Familial hypercholesterolemia in the Finnish north Karelia. A molecular, clinical, and genealogical study.

Vuorio AF, Turtola H, Piilahti KM, Repo P, Kanninen T, Kontula K.

Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3127-38.

PubMed [citation]

PMID:: 9409302

Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia.

Zakharova FM, Damgaard D, Mandelshtam MY, Golubkov VI, Nissen PH, Nilsen GG, Stenderup A, Lipovetsky BM, Konstantinov VO, Denisenko AD, Vasilyev VB, Faergeman O.

BMC Med Genet. 2005 Feb 8;6:6.

PubMed [citation]

PMID:: 15701167
PMCID:: PMC551615

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000024092.2

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

Description

Koivisto et al. (1992) identified a mutation found in many Finnish patients with heterozygous FH (FHCL1; 143890). The mutation, designated FH North Karelia (FH-NK) , deleted 7 nucleotides from exon 6 of the LDLR gene, caused a translational frameshift, and was predicted to result in a truncated receptor protein. The mutation was found in 69 (34%) of 201 unrelated Finnish FH patients and was especially frequent (prevalence 79%) in patients from eastern Finland. FH Helsinki (606945.0029) and FH North Karelia together account for about two-thirds of FH mutations in Finland.

In Finnish North Karelia, with a population of about 180,000, Vuorio et al. (1997) found that the FH-NK mutation accounts for 84% (340 of 407) of FH cases, while the FH-Helsinki allele was found in 4% (18 cases). The minimum prevalence of FH in North Karelia was estimated to be 1 in 441 inhabitants; in 1 commune, a frequency of 1 in 143 was found. By use of parish and tax records, they identified a common ancestor for most of the North Karelian FH-NK persons in the village of Puso, located within an area where the FH prevalence is the highest. DNA analysis indicated that 2% of subjects aged 1 to 25 years would have been diagnosed as false-negative and 7% as false-positive FH patients on the basis of LDL cholesterol determinations alone. Coronary heart disease (CHD) was present in 65 (30%) of the 179 FH gene carriers aged 25 years or more, and 19 individuals had a previous history of acute myocardial infarction. The average age at onset of CHD was 42 years for males and 48 years for females.

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

From LDLR-LOVD, British Heart Foundation, SCV000295060.2

#	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 Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge, SCV000599351.1

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

Description

"Assay Description:Htz patients' fibroblasts, 125-I LDL and RNA assays"

PubMed [ID: 1634609]

#	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	not applicable	not applicable	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum, SCV000606271.1

#	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

Last Updated: Sep 29, 2024

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