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NM_000527.5(LDLR):c.352G>T (p.Asp118Tyr) AND Cardiovascular phenotype

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 6, 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:
RCV002453561.2

Allele description [Variation Report for NM_000527.5(LDLR):c.352G>T (p.Asp118Tyr)]

NM_000527.5(LDLR):c.352G>T (p.Asp118Tyr)

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.352G>T (p.Asp118Tyr)
Other names:
FH Naples-3
HGVS:
  • NC_000019.10:g.11105258G>T
  • NG_009060.1:g.20878G>T
  • NM_000527.5:c.352G>TMANE SELECT
  • NM_001195798.2:c.352G>T
  • NM_001195799.2:c.229G>T
  • NM_001195800.2:c.314-2134G>T
  • NM_001195803.2:c.314-1307G>T
  • NP_000518.1:p.Asp118Tyr
  • NP_000518.1:p.Asp118Tyr
  • NP_001182727.1:p.Asp118Tyr
  • NP_001182728.1:p.Asp77Tyr
  • LRG_274t1:c.352G>T
  • LRG_274:g.20878G>T
  • LRG_274p1:p.Asp118Tyr
  • NC_000019.9:g.11215934G>T
  • NM_000527.4:c.352G>T
  • c.352G>T
  • p.(Asp118Tyr)
Protein change:
D118Y
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001708; dbSNP: rs730882080
NCBI 1000 Genomes Browser:
rs730882080
Molecular consequence:
  • NM_001195800.2:c.314-2134G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1307G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.352G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.352G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.229G>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
unknown functional consequence - Comment(s)

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
SCV002613451Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Oct 6, 2023) 		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

LDL receptor cDNA sequence analysis in familial hypercholesterolemia patients: 5 novel mutations with high prevalence in families originating from southern Italy.

Liguori R, Bianco AM, Argiriou A, Pauciullo P, Giannino A, Rubba P, De Simone V.

Hum Mutat. 2001 May;17(5):433.

PubMed [citation]
PMID:
11317362

Detection of familial hypercholesterolemia in a cohort of children with hypercholesterolemia: results of a family and DNA-based screening.

Campagna F, Martino F, Bifolco M, Montali A, Martino E, Morrone F, Antonini R, Cantafora A, Verna R, Arca M.

Atherosclerosis. 2008 Jan;196(1):356-364. doi: 10.1016/j.atherosclerosis.2006.11.015. Epub 2006 Dec 28.

PubMed [citation]
PMID:
17196209
See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV002613451.2

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

Description

The p.D118Y variant (also known as c.352G>T), located in coding exon 4 of the LDLR gene, results from a G to T substitution at nucleotide position 352. The aspartic acid at codon 118 is replaced by tyrosine, an amino acid with highly dissimilar properties. This alteration, also known as p.D97Y, has been reported primarily in Italian familial hypercholesterolemia (FH) cohorts (Bertolini S et al. Arterioscler. Thromb. Vasc. Biol., 1999 Feb;19:408-18; Liguori R et al. Hum. Mutat., 2001 May;17:433; Campagna F et al. Atherosclerosis, 2008 Jan;196:356-64; Romano M et al. Atherosclerosis, 2010 Jun;210:493-6; Minicocci I et al. J. Pediatr., 2017 Apr;183:100-107.e3; Scicali R et al. Nutr Metab Cardiovasc Dis, 2018 Jan;28:35-43). Reduced LDL-R activity (30% of the control) was reported in a compound heterozygous FH patient who also carried the p.V523M pathogenic mutation (Bertolini S et al. Arterioscler. Thromb. Vasc. Biol., 1999 Feb;19:408-18). Based on internal structural analysis, this variant is predicted to disrupt a linear motif (Ambry internal data). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024