NM_000527.5(LDLR):c.1187del AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 17, 2023
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:: RCV003581655.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1187del]

NM_000527.5(LDLR):c.1187del

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.1187del

HGVS:

NC_000019.10:g.11113278del
NG_009060.1:g.28898del
NM_000527.5:c.1187delMANE SELECT
LRG_274t1:c.1187del
LRG_274:g.28898del
NC_000019.9:g.11223953del
NC_000019.9:g.11223954del
NM_000527.4:c.1187del
NM_000527.4:c.1187delG
p.(Gly396Alafs*17)
p.Gly396Alafs*17

Links:

Molecular consequence:

NM_000527.5:c.1187del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV004272270	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30710474, 20809525, 28645073, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004272270

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 17, 2023)

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

Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio.

Di Taranto MD, de Falco R, Guardamagna O, Massini G, Giacobbe C, Auricchio R, Malamisura B, Proto M, Palma D, Greco L, Fortunato G.

Clin Chem Lab Med. 2019 Jun 26;57(7):1102-1110. doi: 10.1515/cclm-2018-1037.

PubMed [citation]

PMID:: 30710474

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004272270.1

#	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 375810). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 30710474). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly396Alafs*17) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073).

#	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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