NM_000527.5(LDLR):c.589T>G (p.Cys197Gly) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Feb 10, 2023
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:: RCV000490241.4

Allele description [Variation Report for NM_000527.5(LDLR):c.589T>G (p.Cys197Gly)]

NM_000527.5(LDLR):c.589T>G (p.Cys197Gly)

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.589T>G (p.Cys197Gly)

HGVS:

NC_000019.10:g.11105495T>G
NG_009060.1:g.21115T>G
NM_000527.5:c.589T>GMANE SELECT
NM_001195798.2:c.589T>G
NM_001195799.2:c.466T>G
NM_001195800.2:c.314-1897T>G
NM_001195803.2:c.314-1070T>G
NP_000518.1:p.Cys197Gly
NP_000518.1:p.Cys197Gly
NP_001182727.1:p.Cys197Gly
NP_001182728.1:p.Cys156Gly
LRG_274t1:c.589T>G
LRG_274:g.21115T>G
LRG_274p1:p.Cys197Gly
NC_000019.9:g.11216171T>G
NM_000527.4:c.589T>G
c.589T>G

Protein change:

C156G

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001765; dbSNP: rs730882085

NCBI 1000 Genomes Browser:

rs730882085

Molecular consequence:

NM_001195800.2:c.314-1897T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1070T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000527.5:c.589T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.589T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.466T>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000576754	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 10, 2023)	germline	clinical testing	Citation Link,
SCV001469532	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely pathogenic (Sep 9, 2019)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 28964736, 20809525, 18325082, 7603991, 24014831, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000576754

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 10, 2023)

germline

clinical testing

Citation Link,

SCV001469532

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely pathogenic
(Sep 9, 2019)

unknown

clinical testing

PubMed (6)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia.

Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP.

J Clin Lipidol. 2017 Nov-Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4. Erratum in: J Clin Lipidol. 2020 Sep - Oct;14(5):742. doi: 10.1016/j.jacl.2020.09.010..

PubMed [citation]

PMID:: 28964736

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 (6)

Details of each submission

From GeneDx, SCV000576754.5

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as pathogenic or likely pathogenic (ClinVar Variant ID#251308; ClinVar); Not observed at significant frequency in large population cohorts (gnomAD); Also denoted as C176G due to alternate nomenclature; This variant is associated with the following publications: (PMID: 31447099, 28964736, 32143996, 20809525, 34037665, 26582918, 24014831, 27535533, 2988123, 12459547, 9026534, 1301956, 18096825, 20538126, 21276076, 23064986, 27765764, 27816806, 30293936, 33740630, 33994402)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001469532.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Not found in the total gnomAD dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. Other pathogenic or likely pathogenic variants affect the same amino acid. Assessment of experimental evidence suggests this variant results in abnormal protein function.

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

Last Updated: Feb 25, 2025

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