NM_000527.5(LDLR):c.1284del (p.Asn428fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 19, 2020
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:: RCV001537877.3

Allele description [Variation Report for NM_000527.5(LDLR):c.1284del (p.Asn428fs)]

NM_000527.5(LDLR):c.1284del (p.Asn428fs)

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.1284del (p.Asn428fs)

HGVS:

NC_000019.10:g.11113375del
NG_009060.1:g.28995del
NM_000527.5:c.1284delMANE SELECT
NM_001195798.2:c.1284del
NM_001195799.2:c.1161del
NM_001195800.2:c.780del
NM_001195803.2:c.903del
NP_000518.1:p.Asn428fs
NP_001182727.1:p.Asn428fs
NP_001182728.1:p.Asn387fs
NP_001182729.1:p.Asn260fs
NP_001182732.1:p.Asn301fs
LRG_274t1:c.1284del
LRG_274:g.28995del
NC_000019.9:g.11224051del
NM_000527.4:c.1284del
NM_000527.4:c.1284delC

Protein change:

N260fs

Links:

dbSNP: rs2077409930

NCBI 1000 Genomes Browser:

rs2077409930

Molecular consequence:

NM_000527.5:c.1284del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.1284del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.1161del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.780del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.903del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hypercholesterolemia, familial, 1
Synonyms:: LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001754786	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 19, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001754786

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 19, 2020)

germline

clinical testing

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine, SCV001754786.1

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

Description

The c.1284delC (p.Asn428LysfsTer23) frame-shifting variant in the LDLR gene results in a premature translation termination codon. It is predicted to cause loss of normal protein function either through an abnormal, prematurely truncated protein, or by absence of protein product due to nonsense-mediated mRNA decay. This variant has not been observed in the population database (gnomAD). Loss-of-function variants in LDLR gene are known to be pathogenic (PMID: 20809525). For these reasons, this variant c.1284delC (p.Asn428LysfsTer23) of LDLR has been classified as likely pathogenic.

#	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: Oct 8, 2024

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