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NM_000527.5(LDLR):c.1867dup (p.Ile623fs) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 15, 2021
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:
RCV002413665.2

Allele description [Variation Report for NM_000527.5(LDLR):c.1867dup (p.Ile623fs)]

NM_000527.5(LDLR):c.1867dup (p.Ile623fs)

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.1867dup (p.Ile623fs)
HGVS:
  • NC_000019.10:g.11120113dup
  • NG_009060.1:g.35733dup
  • NM_000527.5:c.1867dupMANE SELECT
  • NM_001195798.2:c.1867dup
  • NM_001195799.2:c.1744dup
  • NM_001195800.2:c.1363dup
  • NM_001195803.2:c.1486dup
  • NP_000518.1:p.Ile623fs
  • NP_000518.1:p.Ile623fs
  • NP_001182727.1:p.Ile623fs
  • NP_001182728.1:p.Ile582fs
  • NP_001182729.1:p.Ile455fs
  • NP_001182732.1:p.Ile496fs
  • LRG_274t1:c.1867dup
  • LRG_274:g.35733dup
  • LRG_274p1:p.Ile623fs
  • NC_000019.9:g.11230788_11230789insA
  • NC_000019.9:g.11230789dup
  • NM_000527.4:c.1867dup
  • NM_000527.4:c.1867dupA
Protein change:
I455fs
Links:
dbSNP: rs1555807206
NCBI 1000 Genomes Browser:
rs1555807206
Molecular consequence:
  • NM_000527.5:c.1867dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195798.2:c.1867dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195799.2:c.1744dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195800.2:c.1363dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195803.2:c.1486dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002721035Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 15, 2021) 		germlineclinical testing

PubMed (2)
[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

Molecular genetic testing for autosomal dominant hypercholesterolemia in 29,449 Norwegian index patients and 14,230 relatives during the years 1993-2020.

Leren TP, Bogsrud MP.

Atherosclerosis. 2021 Apr;322:61-66. doi: 10.1016/j.atherosclerosis.2021.02.022. Epub 2021 Feb 23.

PubMed [citation]
PMID:
33740630

Familial Hypercholesterolemia Genetic Variations and Long-Term Cardiovascular Outcomes in Patients with Hypercholesterolemia Who Underwent Coronary Angiography.

Lee WJ, Chuang HN, Chen YM, Liang KW, Tung H, Chen JP, Lee IT, Wang JS, Lin CH, Lin HJ, Sheu WH, Lee WL, Hsiao TH.

Genes (Basel). 2021 Sep 14;12(9). doi:pii: 1413. 10.3390/genes12091413.

PubMed [citation]
PMID:
34573395
PMCID:
PMC8467756

Details of each submission

From Ambry Genetics, SCV002721035.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.1867dupA pathogenic mutation, located in coding exon 13 of the LDLR gene, results from a duplication of A at nucleotide position 1867, causing a translational frameshift with a predicted alternate stop codon (p.I623Nfs*22). This alteration has been reported in association with familial hypercholesterolemia (FH) (Lee WJ et al. Genes (Basel), 2021 Sep;12; Leren TP et al. Atherosclerosis, 2021 04;322:61-66). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024