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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 29, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000810136.10

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; p.Pro309Lysfs*59

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
NM_000527.5:c.925_931del
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:: Familial hypercholesterolemia
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000950326	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 29, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20809525, 1634609, 9409302, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000950326

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 29, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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	clinical testing

Citations

PubMed

Molecular spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network, Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]

PMID:: 20809525
PMCID:: PMC3152176

The familial hypercholesterolemia (FH)-North Karelia mutation of the low density lipoprotein receptor gene deletes seven nucleotides of exon 6 and is a common cause of FH in Finland.

Koivisto UM, Turtola H, Aalto-Setälä K, Top B, Frants RR, Kovanen PT, Syvänen AC, Kontula K.

J Clin Invest. 1992 Jul;90(1):219-28.

PubMed [citation]

PMID:: 1634609
PMCID:: PMC443084

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000950326.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). This sequence change creates a premature translational stop signal (p.Pro309Lysfs*59) in the LDLR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with¬†familial hypercholesterolemia¬†in multiple families (PMID: 1634609, 9409302).¬†This variant is also known as a founder mutation¬†FH-North Karelia¬†in the literature.¬†ClinVar contains an entry for this variant (Variation ID:¬†3729).

#	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: Feb 25, 2025

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