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NM_000527.5(LDLR):c.1865A>G (p.Asp622Gly) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 20, 2017
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:
RCV002411100.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1865A>G (p.Asp622Gly)]

NM_000527.5(LDLR):c.1865A>G (p.Asp622Gly)

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.1865A>G (p.Asp622Gly)
HGVS:
  • NC_000019.10:g.11120111A>G
  • NG_009060.1:g.35731A>G
  • NM_000527.5:c.1865A>GMANE SELECT
  • NM_001195798.2:c.1865A>G
  • NM_001195799.2:c.1742A>G
  • NM_001195800.2:c.1361A>G
  • NM_001195803.2:c.1484A>G
  • NP_000518.1:p.Asp622Gly
  • NP_000518.1:p.Asp622Gly
  • NP_001182727.1:p.Asp622Gly
  • NP_001182728.1:p.Asp581Gly
  • NP_001182729.1:p.Asp454Gly
  • NP_001182732.1:p.Asp495Gly
  • LRG_274t1:c.1865A>G
  • LRG_274:g.35731A>G
  • LRG_274p1:p.Asp622Gly
  • NC_000019.9:g.11230787A>G
  • NM_000527.4:c.1865A>G
  • c.1865A>G
Protein change:
D454G
Links:
LDLR-LOVD, British Heart Foundation: LDLR_000256; dbSNP: rs879255060
NCBI 1000 Genomes Browser:
rs879255060
Molecular consequence:
  • NM_000527.5:c.1865A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.1865A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.1742A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.1361A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.1484A>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
SCV002720968Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 20, 2017) 		germlineclinical testing

PubMed (6)
[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

Familial hypercholesterolemia in St-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia.

Zakharova FM, Damgaard D, Mandelshtam MY, Golubkov VI, Nissen PH, Nilsen GG, Stenderup A, Lipovetsky BM, Konstantinov VO, Denisenko AD, Vasilyev VB, Faergeman O.

BMC Med Genet. 2005 Feb 8;6:6.

PubMed [citation]
PMID:
15701167
PMCID:
PMC551615

Genetic screening protocol for familial hypercholesterolemia which includes splicing defects gives an improved mutation detection rate.

Graham CA, McIlhatton BP, Kirk CW, Beattie ED, Lyttle K, Hart P, Neely RD, Young IS, Nicholls DP.

Atherosclerosis. 2005 Oct;182(2):331-40.

PubMed [citation]
PMID:
16159606
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV002720968.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The p.D622G pathogenic mutation (also known as c.1865A>G), located in coding exon 13 of the LDLR gene, results from an A to G substitution at nucleotide position 1865. The aspartic acid at codon 622 is replaced by glycine, an amino acid with similar properties. This alteration has been described in individuals with familial hypercholesterolemia (FH) (Alonso R et al. Clin. Biochem., 2009 Jun;42:899-903; Tichý L et al. Atherosclerosis, 2012 Aug;223:401-8). In addition, alterations affecting the same amino acid residue, p.D622N, p.D622Y, and p.D622A, have also been reported in FH cases (Zakharova FM et al. BMC Med. Genet., 2005 Feb;6:6; Graham CA et al. Atherosclerosis, 2005 Oct;182:331-40; Jiang L et al. J. Clin. Lipidol., 2015 Dec;10:538-546.e5). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 1, 2024