NM_000527.5(LDLR):c.1055G>A (p.Cys352Tyr) AND LDLR-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 5, 2023
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV003952374.3

Allele description [Variation Report for NM_000527.5(LDLR):c.1055G>A (p.Cys352Tyr)]

NM_000527.5(LDLR):c.1055G>A (p.Cys352Tyr)

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.1055G>A (p.Cys352Tyr)

Other names:

NM_000527.5(LDLR):c.1055G>A

HGVS:

NC_000019.10:g.11110766G>A
NG_009060.1:g.26386G>A
NM_000527.5:c.1055G>AMANE SELECT
NM_001195798.2:c.1055G>A
NM_001195799.2:c.932G>A
NM_001195800.2:c.551G>A
NM_001195803.2:c.674G>A
NP_000518.1:p.Cys352Tyr
NP_000518.1:p.Cys352Tyr
NP_001182727.1:p.Cys352Tyr
NP_001182728.1:p.Cys311Tyr
NP_001182729.1:p.Cys184Tyr
NP_001182732.1:p.Cys225Tyr
LRG_274t1:c.1055G>A
LRG_274:g.26386G>A
LRG_274p1:p.Cys352Tyr
NC_000019.9:g.11221442G>A
NM_000527.4:c.1055G>A
P01130:p.Cys352Tyr
c.1055G>A

Protein change:

C184Y

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001339; UniProtKB: P01130#VAR_005369; dbSNP: rs193922566

Molecular consequence:

NM_000527.5:c.1055G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1055G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.932G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.551G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.674G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: LDLR-related disorder
Synonyms:: LDLR-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004767085	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Likely pathogenic (Nov 5, 2023)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004767085

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Likely pathogenic
(Nov 5, 2023)

germline

clinical testing

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004767085.2

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

Description

The LDLR c.1055G>A variant is predicted to result in the amino acid substitution p.Cys352Tyr. This variant was reported in patients with hypercholesterolemia (For example, reported as FH Mexico-2 or C331Y in Hobbs et al. 1992. PubMed ID: 1301956; Sturm. 2021. PubMed ID: 34037665). Incomplete penetrance was noted in a family (Magaña Torres et al. 2014. PubMed ID: 25234566). Of note, other missense variants affecting the same amino acid (p.Cys352Ser, p.Cys352Arg, p.Cys352Phe) have also been reported as causative for hypercholesterolemia (HGMD database; Hobbs et al. 1992. PubMed ID: 1301956). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-11221442-G-A). This variant is interpreted as likely pathogenic or pathogenic in the ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/RCV000030122.12/). This variant is interpreted as likely pathogenic.

#	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: Aug 4, 2026

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