NM_000527.5(LDLR):c.41T>A (p.Leu14Ter) AND Familial hypercholesterolemia

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 28, 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:: RCV000822108.6

Allele description

NM_000527.5(LDLR):c.41T>A (p.Leu14Ter)

Genes:

LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.41T>A (p.Leu14Ter)

HGVS:

NC_000019.10:g.11089589T>A
NG_009060.1:g.5209T>A
NM_000527.5:c.41T>AMANE SELECT
NM_001195798.2:c.41T>A
NM_001195799.2:c.41T>A
NM_001195800.2:c.41T>A
NM_001195803.2:c.41T>A
NP_000518.1:p.Leu14Ter
NP_000518.1:p.Leu14Ter
NP_001182727.1:p.Leu14Ter
NP_001182728.1:p.Leu14Ter
NP_001182729.1:p.Leu14Ter
NP_001182732.1:p.Leu14Ter
LRG_274t1:c.41T>A
LRG_274:g.5209T>A
LRG_274p1:p.Leu14Ter
NC_000019.9:g.11200265T>A
NM_000527.4:c.41T>A
NR_163945.1:n.71A>T

Protein change:

L14*

Links:

dbSNP: rs1600683731

NCBI 1000 Genomes Browser:

rs1600683731

Molecular consequence:

NR_163945.1:n.71A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000527.5:c.41T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.41T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.41T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.41T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195803.2:c.41T>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000962894	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 28, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20809525, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000962894

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 28, 2019)

germline

clinical testing

PubMed (2)
[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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000962894.6

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

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 variant has not been reported in the literature in individuals with LDLR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu14*) in the LDLR gene. It is expected to result in an absent or disrupted protein product.

#	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 1, 2024

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