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NM_000527.5(LDLR):c.1284C>G (p.Asn428Lys) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 20, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV004020963.1

Allele description [Variation Report for NM_000527.5(LDLR):c.1284C>G (p.Asn428Lys)]

NM_000527.5(LDLR):c.1284C>G (p.Asn428Lys)

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.1284C>G (p.Asn428Lys)
Other names:
NM_000527.5(LDLR):c.1284C>G; p.Asn428Lys
HGVS:
  • NC_000019.10:g.11113375C>G
  • NG_009060.1:g.28995C>G
  • NM_000527.5:c.1284C>GMANE SELECT
  • NM_001195798.2:c.1284C>G
  • NM_001195799.2:c.1161C>G
  • NM_001195800.2:c.780C>G
  • NM_001195803.2:c.903C>G
  • NP_000518.1:p.Asn428Lys
  • NP_000518.1:p.Asn428Lys
  • NP_001182727.1:p.Asn428Lys
  • NP_001182728.1:p.Asn387Lys
  • NP_001182729.1:p.Asn260Lys
  • NP_001182732.1:p.Asn301Lys
  • LRG_274t1:c.1284C>G
  • LRG_274:g.28995C>G
  • LRG_274p1:p.Asn428Lys
  • NC_000019.9:g.11224051C>G
  • NM_000527.4:c.1284C>G
  • c.1284C>G
Protein change:
N260K
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000540; dbSNP: rs368708058
NCBI 1000 Genomes Browser:
rs368708058
Molecular consequence:
  • NM_000527.5:c.1284C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1284C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1161C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.780C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.903C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003907261Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Mar 20, 2023) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Low-density lipoprotein receptor gene mutations in a Southeast Asian population with familial hypercholesterolemia.

Khoo KL, van Acker P, Defesche JC, Tan H, van de Kerkhof L, Heijnen-van Eijk SJ, Kastelein JJ, Deslypere JP.

Clin Genet. 2000 Aug;58(2):98-105.

PubMed [citation]
PMID:
11005141

Compound heterozygous familial hypercholesterolemia and familial defective apolipoprotein B-100 produce exaggerated hypercholesterolemia.

Tai ES, Koay ES, Chan E, Seng TJ, Loh LM, Sethi SK, Tan CE.

Clin Chem. 2001 Mar;47(3):438-43.

PubMed [citation]
PMID:
11238294
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV003907261.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The c.1284C>G (p.N428K) alteration is located in exon 9 (coding exon 9) of the LDLR gene. This alteration results from a C to G substitution at nucleotide position 1284, causing the asparagine (N) at amino acid position 428 to be replaced by a lysine (K). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant (also referred to as p.N407K) has been detected in several unrelated individuals with familial hypercholesterolemia (FH) (Khoo, 2000; Fouchier, 2001; van der Graaf, 2011; García-García, 2001; Bunn, 2002; Rimbert, 2021; Razman, 2022). This variant has also been detected in additional FH and dyslipidemia cohorts (Vergotine, 2001; Murdock, 2021). In one study, this variant co-occurred with an APOB variant in a proband reported to have more severe hypercholesterolemia than relatives with only one variant (Tai, 2001; Taylor, 2010). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

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

Last Updated: Nov 10, 2024