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NM_000527.5(LDLR):c.1294C>G (p.Leu432Val) AND LDLR-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 25, 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:
RCV003895079.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1294C>G (p.Leu432Val)]

NM_000527.5(LDLR):c.1294C>G (p.Leu432Val)

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.1294C>G (p.Leu432Val)
HGVS:
  • NC_000019.10:g.11113385C>G
  • NG_009060.1:g.29005C>G
  • NM_000527.5:c.1294C>GMANE SELECT
  • NM_001195798.2:c.1294C>G
  • NM_001195799.2:c.1171C>G
  • NM_001195800.2:c.790C>G
  • NM_001195803.2:c.913C>G
  • NP_000518.1:p.Leu432Val
  • NP_000518.1:p.Leu432Val
  • NP_001182727.1:p.Leu432Val
  • NP_001182728.1:p.Leu391Val
  • NP_001182729.1:p.Leu264Val
  • NP_001182732.1:p.Leu305Val
  • LRG_274t1:c.1294C>G
  • LRG_274:g.29005C>G
  • LRG_274p1:p.Leu432Val
  • NC_000019.9:g.11224061C>G
  • NM_000527.4:c.1294C>G
  • P01130:p.Leu432Val
  • c.1294C>G
Protein change:
L264V
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000541; UniProtKB: P01130#VAR_007988; dbSNP: rs730882100
NCBI 1000 Genomes Browser:
rs730882100
Molecular consequence:
  • NM_000527.5:c.1294C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1294C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1171C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.790C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.913C>G - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
no known functional consequence - Comment(s)

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
SCV004717204PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Uncertain significance
(Nov 25, 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, SCV004717204.2

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

Description

The LDLR c.1294C>G variant is predicted to result in the amino acid substitution p.Leu432Val. This variant has also been reported in individuals with hypercholesterolemia and in controls in different reports (Thormaehlen et al. 2015. PubMed ID: 25647241; Do et al. 2015. PubMed ID: 25487149). It was also found in one individual who harbored the c.1393T>A (p.Tyr465Asn) variant that is also found in this patient, and it was suggested that together the two variants may form a hypomorphic allele, but further studies to confirm they are on the same allele were not performed (Thormaehlen et al. 2015. PubMed ID: 25647241). This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD. This variant has been reported in ClinVar with interpretations of uncertain significance, likely pathogenic, and pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/183111/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: Oct 26, 2024