NM_000527.5(LDLR):c.2430G>A (p.Trp810Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 17, 2021
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:: RCV000483979.27

Allele description [Variation Report for NM_000527.5(LDLR):c.2430G>A (p.Trp810Ter)]

NM_000527.5(LDLR):c.2430G>A (p.Trp810Ter)

Gene:

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.2430G>A (p.Trp810Ter)

HGVS:

NC_000019.10:g.11129553G>A
NG_009060.1:g.45173G>A
NM_000527.5:c.2430G>AMANE SELECT
NM_001195798.2:c.2430G>A
NM_001195799.2:c.2307G>A
NM_001195800.2:c.1926G>A
NM_001195803.2:c.1896G>A
NP_000518.1:p.Trp810Ter
NP_000518.1:p.Trp810Ter
NP_001182727.1:p.Trp810Ter
NP_001182728.1:p.Trp769Ter
NP_001182729.1:p.Trp642Ter
NP_001182732.1:p.Trp632Ter
LRG_274t1:c.2430G>A
LRG_274:g.45173G>A
LRG_274p1:p.Trp810Ter
NC_000019.9:g.11240229G>A
NM_000527.4:c.2430G>A
c.2430G>A

Protein change:

W632*

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001088; dbSNP: rs879255210

NCBI 1000 Genomes Browser:

rs879255210

Molecular consequence:

NM_000527.5:c.2430G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195798.2:c.2430G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195799.2:c.2307G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195800.2:c.1926G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195803.2:c.1896G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568514	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 19, 2017)	germline	clinical testing	Citation Link,
SCV001246013	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jan 1, 2019)	germline	clinical testing	Citation Link,
SCV001762193	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568514

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 19, 2017)

germline

clinical testing

Citation Link,

SCV001246013

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jan 1, 2019)

germline

clinical testing

Citation Link,

SCV001762193

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 17, 2021)

germline

clinical testing

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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000568514.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The W810X variant in the LDLR gene has been reported as a novel variant in one patient with FH (Fouchier et al., 2005). This variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the LDLR gene have been reported in Human Gene Mutation Database in association with FH (Stenson et al., 2014). Furthermore, the W810X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server)

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV001246013.27

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	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		1	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001762193.1

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

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

Last Updated: Mar 11, 2025

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