VCV000251209.1 - ClinVar

NM_000527.5(LDLR):c.415G>A (p.Asp139Asn)

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.

(3)

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.

Likely 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.415G>A (p.Asp139Asn)

Variation ID: 251209 Accession: VCV000251209.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.2 19: 11105321 (GRCh38) [ NCBI UCSC ] 19: 11215997 (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	Aug 13, 2017	May 30, 2018	Mar 25, 2016

HGVS

Nucleotide	Protein	Molecular consequence
NM_000527.5:c.415G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000518.1:p.Asp139Asn	missense
NM_001195798.2:c.415G>A	NP_001182727.1:p.Asp139Asn	missense
NM_001195799.2:c.292G>A	NP_001182728.1:p.Asp98Asn	missense
NM_001195800.2:c.314-2071G>A		intron variant
NM_001195803.2:c.314-1244G>A		intron variant
NC_000019.10:g.11105321G>A
NC_000019.9:g.11215997G>A
NG_009060.1:g.20941G>A
LRG_274:g.20941G>A
LRG_274t1:c.415G>A	LRG_274p1:p.Asp139Asn

... more HGVS ... less HGVS

Protein change

D139N, D98N

Other names

FH Sassari-2

Canonical SPDI

NC_000019.10:11105320:G:A

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: CA10584907 LDLR-LOVD, British Heart Foundation: LDLR_000413 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	Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Mar 25, 2016	RCV000237450.5

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.
Likely 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: SCV000294693.2 First in ClinVar: Jul 29, 2016 Last updated: May 30, 2018	Publications: PubMed (2) PubMed: 10634824‚ 17539906 Observation 1: Number of individuals with the variant: 1 Observation 2: Number of individuals with the variant: 1
Likely pathogenic (Mar 01, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Familial hypercholesterolemia (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Laboratory of Genetics and Molecular Cardiology, University of São Paulo Study: HipercolBrasil Accession: SCV000588498.1 First in ClinVar: Aug 13, 2017 Last updated: Aug 13, 2017
Pathogenic (-)	no assertion criteria provided Method: research	Familial hypercholesterolemia Affected status: unknown Allele origin: germline	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum Accession: SCV000606109.1 First in ClinVar: Aug 13, 2017 Last updated: Aug 13, 2017

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
Multiplex ARMS analysis to detect 13 common mutations in familial hypercholesterolaemia.	Taylor A	Clinical genetics	2007	PMID: 17539906
Influence of beta(0)-thalassemia on the phenotypic expression of heterozygous familial hypercholesterolemia : a study of patients with familial hypercholesterolemia from Sardinia.	Deiana L	Arteriosclerosis, thrombosis, and vascular biology	2000	PMID: 10634824

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_000527.5(LDLR):c.415G>A (p.Asp139Asn)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...