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NM_000527.5(LDLR):c.1730G>C (p.Trp577Ser) AND LDLR-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 22, 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:
RCV003897581.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1730G>C (p.Trp577Ser)]

NM_000527.5(LDLR):c.1730G>C (p.Trp577Ser)

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.1730G>C (p.Trp577Ser)
HGVS:
  • NC_000019.10:g.11116883G>C
  • NG_009060.1:g.32503G>C
  • NM_000527.5:c.1730G>CMANE SELECT
  • NM_001195798.2:c.1730G>C
  • NM_001195799.2:c.1607G>C
  • NM_001195800.2:c.1226G>C
  • NM_001195803.2:c.1349G>C
  • NP_000518.1:p.Trp577Ser
  • NP_000518.1:p.Trp577Ser
  • NP_001182727.1:p.Trp577Ser
  • NP_001182728.1:p.Trp536Ser
  • NP_001182729.1:p.Trp409Ser
  • NP_001182732.1:p.Trp450Ser
  • LRG_274t1:c.1730G>C
  • LRG_274:g.32503G>C
  • LRG_274p1:p.Trp577Ser
  • NC_000019.9:g.11227559G>C
  • NM_000527.4:c.1730G>C
  • P01130:p.Trp577Ser
  • c.1730G>C
Protein change:
W409S
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001507; UniProtKB: P01130#VAR_072854; dbSNP: rs138947766
NCBI 1000 Genomes Browser:
rs138947766
Molecular consequence:
  • NM_000527.5:c.1730G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1730G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1607G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1226G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1349G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004711912PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Nov 22, 2023) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004711912.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The LDLR c.1730G>C variant is predicted to result in the amino acid substitution p.Trp577Ser. This variant (also known as W556S) was reported in individuals with autosomal dominant familial hypercholesterolemia (Fouchier et al. 2001. PubMed ID: 11810272; Table S1, Benedek et al. 2021. PubMed ID: 33955087; Table S1, Leren et al. 2021. PubMed ID: 33740630; Table 2, Miroshnikova et al. 2021. PubMed ID: 33269076). Other missense variants impacting this residue (p.Trp577Gly, p.Trp577Cys, p.Trp577Arg) have also been reported as pathogenic in individuals with hypercholesterolemia phenotypes (Table S1, Leren et al. 2021. PubMed ID: 33740630; eTable 1, Sturm. 2021. PubMed ID: 34037665). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024