NM_000527.5(LDLR):c.2500del (p.Asp834fs) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV004023447.1

Allele description [Variation Report for NM_000527.5(LDLR):c.2500del (p.Asp834fs)]

NM_000527.5(LDLR):c.2500del (p.Asp834fs)

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.2500del (p.Asp834fs)

HGVS:

NC_000019.10:g.11129623del
NG_009060.1:g.45243del
NM_000527.5:c.2500delMANE SELECT
NM_001195798.2:c.2500del
NM_001195799.2:c.2377del
NM_001195800.2:c.1996del
NM_001195803.2:c.1966del
NP_000518.1:p.Asp834fs
NP_000518.1:p.Asp834fs
NP_001182727.1:p.Asp834fs
NP_001182728.1:p.Asp793fs
NP_001182729.1:p.Asp666fs
NP_001182732.1:p.Asp656fs
LRG_274t1:c.2500del
LRG_274:g.45243del
LRG_274p1:p.Asp834fs
NC_000019.9:g.11240298del
NC_000019.9:g.11240299del
NM_000527.4:c.2500del
NM_000527.4:c.2500delG

Protein change:

D656fs

Links:

dbSNP: rs1555809594

NCBI 1000 Genomes Browser:

rs1555809594

Molecular consequence:

NM_000527.5:c.2500del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.2500del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.2377del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1996del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1966del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005035838	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005035838

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 31, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Details of each submission

From Ambry Genetics, SCV005035838.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The c.2500delG variant, located in coding exon 17 of the LDLR gene, results from a deletion of one nucleotide at nucleotide position 2500, causing a translational frameshift with a predicted alternate stop codon (p.D834Mfs*95). This alteration occurs at the 3' terminus of theLDLR gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 3% of the protein. The exact functional effect of this alteration is unknown. This alteration has been reported in a hypercholesterolemia cohort; however, clinical details were limited (Leren TP et al. Atherosclerosis, 2021 Apr;322:61-66). Based on the available evidence, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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