VCV000251182.4 - ClinVar

NM_000527.5(LDLR):c.369_370del (p.Arg124fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000527.5(LDLR):c.369_370del (p.Arg124fs)

Variation ID: 251182 Accession: VCV000251182.4

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: 19p13.2 19: 11105271-11105272 (GRCh38) [ NCBI UCSC ] 19: 11215947-11215948 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 15, 2016	Jun 8, 2021	May 24, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_000527.5:c.369_370del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000518.1:p.Arg124fs	frameshift
NM_000527.4:c.369_370delTC
NM_001195798.2:c.369_370del	NP_001182727.1:p.Arg124fs	frameshift
NM_001195799.2:c.246_247del	NP_001182728.1:p.Arg83fs	frameshift
NM_001195800.2:c.314-2121TC[2]		intron variant
NM_001195803.2:c.314-1294TC[2]		intron variant
NC_000019.10:g.11105271TC[2]
NC_000019.9:g.11215947TC[2]
NG_009060.1:g.20891TC[2]
NG_009060.1:g.20895_20896del
LRG_274:g.20891TC[2]

... more HGVS ... less HGVS

Protein change

R83fs, R124fs

Other names

Canonical SPDI

NC_000019.10:11105270:TCTCTC:TCTC

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA10584881 LDLR-LOVD, British Heart Foundation: LDLR_000691 dbSNP: rs879254496 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
LDLR		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4076	4352

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hypercholesterolemia, familial, 1	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	May 24, 2021	RCV000238184.14

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 25, 2016)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: literature only	Familial hypercholesterolemia (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	LDLR-LOVD, British Heart Foundation Accession: SCV000294663.2 First in ClinVar: Jul 29, 2016 Last updated: Oct 15, 2016	Publications: PubMed (2) PubMed: 10422804‚ 21310417 Observation 1: Number of individuals with the variant: 1 Observation 2: Number of individuals with the variant: 1
Pathogenic (Mar 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Familial hypercholesterolemia (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge Accession: SCV000322895.1 First in ClinVar: Oct 15, 2016 Last updated: Oct 15, 2016	Comment: 0/190 non-FH alleles Observation 1: Observation 2:
Pathogenic (Nov 05, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercholesterolemia, familial, 1 (Autosomal dominant inheritance) Affected status: yes Allele origin: unknown	Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation Additional submitter: Centre of Molecular Biology and Gene Therapy, University Hospital Brno Accession: SCV000540728.1 First in ClinVar: Oct 15, 2016 Last updated: Oct 15, 2016 Comment: This variant was referred in PMID: 22698793 as p.(Ser123fs*6).	Publications: PubMed (1) PubMed: 22698793 Number of individuals with the variant: 1 Clinical Features: Hypercholesterolemia (present) Age: 60-69 years Sex: male Ethnicity/Population group: Caucasian Geographic origin: Czech Republic Tissue: Whole blood
Pathogenic (May 24, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hypercholesterolemia, familial, 1 Affected status: yes Allele origin: germline	Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II Accession: SCV001653590.1 First in ClinVar: Jun 08, 2021 Last updated: Jun 08, 2021	Publications: PubMed (2) PubMed: 10422804‚ 30710474 Number of individuals with the variant: 1 Ethnicity/Population group: Caucasian Geographic origin: Italy

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio.	Di Taranto MD	Clinical chemistry and laboratory medicine	2019	PMID: 30710474
The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotype-phenotype correlations.	Tichý L	Atherosclerosis	2012	PMID: 22698793
An APEX-based genotyping microarray for the screening of 168 mutations associated with familial hypercholesterolemia.	Dušková L	Atherosclerosis	2011	PMID: 21310417
Founder mutations in the LDL receptor gene contribute significantly to the familial hypercholesterolemia phenotype in the indigenous South African population of mixed ancestry.	Loubser O	Clinical genetics	1999	PMID: 10422804

Text-mined citations for rs879254496 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_000527.5(LDLR):c.369_370del (p.Arg124fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs879254496 ...