NM_000527.5(LDLR):c.244_246del (p.Cys82del) AND Familial hypercholesterolemia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 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:: RCV000774815.4

Allele description [Variation Report for NM_000527.5(LDLR):c.244_246del (p.Cys82del)]

NM_000527.5(LDLR):c.244_246del (p.Cys82del)

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.244_246del (p.Cys82del)

HGVS:

NC_000019.10:g.11102717_11102719del
NG_009060.1:g.18337_18339del
NM_000527.5:c.244_246delMANE SELECT
NM_001195798.2:c.244_246del
NM_001195799.2:c.190+2372_190+2374del
NM_001195800.2:c.244_246del
NM_001195803.2:c.244_246del
NP_000518.1:p.Cys82del
NP_000518.1:p.Cys82del
NP_001182727.1:p.Cys82del
NP_001182729.1:p.Cys82del
NP_001182732.1:p.Cys82del
LRG_274t1:c.244_246del
LRG_274:g.18337_18339del
LRG_274p1:p.Cys82del
NC_000019.10:g.11102717_11102719delTGC
NC_000019.9:g.11213393_11213395del
NM_000527.4:c.244_246del
NM_000527.4:c.244_246delTGC

Protein change:

C82del

Links:

dbSNP: rs1568591929

NCBI 1000 Genomes Browser:

rs1568591929

Molecular consequence:

NM_000527.5:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195798.2:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195800.2:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195803.2:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001195799.2:c.190+2372_190+2374del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Familial hypercholesterolemia
Identifiers:: MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

Recent activity

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RecName: Full=Advillin; AltName: Full=p92
RecName: Full=Advillin; AltName: Full=p92
gi|313104246|sp|O75366.3|AVIL_HUMAN

Protein
RecName: Full=Olfactory receptor 51H1; AltName: Full=Olfactory receptor OR11-25
RecName: Full=Olfactory receptor 51H1; AltName: Full=Olfactory receptor OR11-25
gi|38372818|sp|Q8NH63.1|O51H1_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000908834	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 15, 2021)	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

SCV000908834

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 15, 2021)

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 Color Diagnostics, LLC DBA Color Health, SCV000908834.3

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

Description

This variant (also known as p.Cys61del in the mature protein) is a single amino acid deletion in the second LDLR type A repeat of the ligand binding domain of the LDLR protein. Although functional studies have not been reported, this variant changes one of the functionally critical cysteine residues that form intra-repeat disulfide bonds in the ligand binding domain (PMID: 2088165, 6091915, 15952897) and is expected to have deleterious impact on the LDLR protein folding and stability. To our knowledge, the variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on available evidence, this variant is 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: Sep 1, 2024

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