NM_000527.5(LDLR):c.233del (p.Arg78fs) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 24, 2021
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:: RCV000408851.3

Allele description [Variation Report for NM_000527.5(LDLR):c.233del (p.Arg78fs)]

NM_000527.5(LDLR):c.233del (p.Arg78fs)

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.233del (p.Arg78fs)

HGVS:

NC_000019.10:g.11102706del
NG_009060.1:g.18326del
NM_000527.5:c.233delMANE SELECT
NM_001195798.2:c.233del
NM_001195799.2:c.190+2361del
NM_001195800.2:c.233del
NM_001195803.2:c.233del
NP_000518.1:p.Arg78fs
NP_000518.1:p.R78Lfs*127
NP_001182727.1:p.Arg78fs
NP_001182729.1:p.Arg78fs
NP_001182732.1:p.Arg78fs
LRG_274:g.18326del
NC_000019.10:g.11102706delG
NC_000019.9:g.11213382del
NM_000527.4:c.233delG
NM_000527.5:c.233delGMANE SELECT
p.(Arg78Leufs*128)

Protein change:

R78fs

Links:

dbSNP: rs1057516129

NCBI 1000 Genomes Browser:

rs1057516129

Molecular consequence:

NM_000527.5:c.233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.190+2361del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV000484802	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]
SCV001653584	Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28008009, 32041611, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000484802

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]

SCV001653584

Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 24, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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
Caucasian	germline	yes	2	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

Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study.

Dewey FE, Murray MF, Overton JD, Habegger L, Leader JB, Fetterolf SN, O'Dushlaine C, Van Hout CV, Staples J, Gonzaga-Jauregui C, Metpally R, Pendergrass SA, Giovanni MA, Kirchner HL, Balasubramanian S, Abul-Husn NS, Hartzel DN, Lavage DR, Kost KA, Packer JS, Lopez AE, Penn J, et al.

Science. 2016 Dec 23;354(6319). doi:pii: aaf6814. 10.1126/science.aaf6814.

PubMed [citation]

PMID:: 28008009

See all PubMed Citations (4)

Details of each submission

From Robarts Research Institute, Western University, SCV000484802.1

#	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 Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II, SCV001653584.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	2	not provided	not provided	clinical testing	PubMed (3)

#	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		2	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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