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NM_000527.5(LDLR):c.1816G>A (p.Ala606Thr) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 27, 2022
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:
RCV002411092.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1816G>A (p.Ala606Thr)]

NM_000527.5(LDLR):c.1816G>A (p.Ala606Thr)

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.1816G>A (p.Ala606Thr)
Other names:
NM_000527.5(LDLR):c.1816G>A
HGVS:
  • NC_000019.10:g.11116969G>A
  • NG_009060.1:g.32589G>A
  • NM_000527.5:c.1816G>AMANE SELECT
  • NM_001195798.2:c.1816G>A
  • NM_001195799.2:c.1693G>A
  • NM_001195800.2:c.1312G>A
  • NM_001195803.2:c.1435G>A
  • NP_000518.1:p.Ala606Thr
  • NP_000518.1:p.Ala606Thr
  • NP_001182727.1:p.Ala606Thr
  • NP_001182728.1:p.Ala565Thr
  • NP_001182729.1:p.Ala438Thr
  • NP_001182732.1:p.Ala479Thr
  • LRG_274t1:c.1816G>A
  • LRG_274:g.32589G>A
  • LRG_274p1:p.Ala606Thr
  • NC_000019.9:g.11227645G>A
  • NM_000527.4:c.1816G>A
  • c.1816G>A
Protein change:
A438T
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001527; dbSNP: rs72658865
NCBI 1000 Genomes Browser:
rs72658865
Molecular consequence:
  • NM_000527.5:c.1816G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1816G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1693G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1312G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1435G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002711992Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jan 27, 2022) 		germlineclinical testing

PubMed (7)
[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

Mutations in low-density lipoprotein receptor gene as a cause of hypercholesterolemia in Taiwan.

Chiu CY, Wu YC, Jenq SF, Jap TS.

Metabolism. 2005 Aug;54(8):1082-6.

PubMed [citation]
PMID:
16092059

Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform.

Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P.

Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6.

PubMed [citation]
PMID:
19318025
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002711992.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The p.A606T variant (also known as c.1816G>A), located in coding exon 12 of the LDLR gene, results from a G to A substitution at nucleotide position 1816. The alanine at codon 606 is replaced by threonine, an amino acid with similar properties. This alteration, which is also known as p.A585T, has been reported in familial hypercholesterolemia (FH) cohorts; however, clinical details were limited in some cases (Chiu CY et al. Metabolism, 2005 Aug;54:1082-6; Alonso R et al. Clin Biochem, 2009 Jun;42:899-903; Viladés Medel D et al. Am. J. Cardiol., 2013 Apr;111:955-61; Sánchez-Hernández RM et al. Circ Cardiovasc Genet, 2016 Dec;9:504-510; Ibarretxe D et al. Atherosclerosis, 2018 11;278:210-216; Ma Y et al. J Clin Lipidol 2018 Oct;12:230-235.e6; Lamiquiz-Moneo I et al. Rev Esp Cardiol (Engl Ed), 2021 Aug;74:664-673). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Sep 29, 2024