NM_000527.5(LDLR):c.905del (p.Cys302fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Feb 22, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000408896.4

Allele description [Variation Report for NM_000527.5(LDLR):c.905del (p.Cys302fs)]

NM_000527.5(LDLR):c.905del (p.Cys302fs)

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.905del (p.Cys302fs)

HGVS:

NC_000019.10:g.11107479del
NG_009060.1:g.23099del
NM_000527.4:c.905del
NM_000527.5:c.905delMANE SELECT
NM_001195798.2:c.905del
NM_001195799.2:c.782del
NM_001195800.2:c.401del
NM_001195803.2:c.524del
NP_000518.1:p.C302Sfs*67
NP_000518.1:p.Cys302fs
NP_001182727.1:p.Cys302fs
NP_001182728.1:p.Cys261fs
NP_001182729.1:p.Cys134fs
NP_001182732.1:p.Cys175fs
LRG_274t1:c.905del
LRG_274:g.23099del
NC_000019.9:g.11218155del
NM_000527.4:c.905delG

Protein change:

C134fs

Links:

dbSNP: rs1057516130

NCBI 1000 Genomes Browser:

rs1057516130

Molecular consequence:

NM_000527.5:c.905del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.905del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.401del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.524del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV000484803	Robarts Research Institute, Western University	criteria provided, single submitter (Wang et al. (Arterioscler Thromb Vasc Biol. 2016))	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003830896	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 22, 2022)	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

SCV000484803

Robarts Research Institute, Western University

criteria provided, single submitter

(Wang et al. (Arterioscler Thromb Vasc Biol. 2016))

Likely pathogenic

germline

clinical testing

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

SCV003830896

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 22, 2022)

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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Polygenic Versus Monogenic Causes of Hypercholesterolemia Ascertained Clinically.

Wang J, Dron JS, Ban MR, Robinson JF, McIntyre AD, Alazzam M, Zhao PJ, Dilliott AA, Cao H, Huff MW, Rhainds D, Low-Kam C, Dubé MP, Lettre G, Tardif JC, Hegele RA.

Arterioscler Thromb Vasc Biol. 2016 Dec;36(12):2439-2445. Epub 2016 Oct 20.

PubMed [citation]

PMID:: 27765764

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 Robarts Research Institute, Western University, SCV000484803.1

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

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

From Revvity Omics, Revvity, SCV003830896.2

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

#	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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