VCV000251807.4 - ClinVar

NM_000527.5(LDLR):c.1359-29G>A

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Likely benign
Likely benign (3)

3 out of 3 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000527.5(LDLR):c.1359-29G>A

Variation ID: 251807 Accession: VCV000251807.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19p13.2 19: 11113506 (GRCh38) [ NCBI UCSC ] 19: 11224182 (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	Jul 29, 2016	Jan 13, 2025	Aug 7, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000527.5:c.1359-29G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001195798.2:c.1359-29G>A		intron variant
NM_001195799.2:c.1236-29G>A		intron variant
NM_001195800.2:c.855-29G>A		intron variant
NM_001195803.2:c.978-29G>A		intron variant
NR_106946.1:n.33G>A		non-coding transcript variant
NC_000019.10:g.11113506G>A
NC_000019.9:g.11224182G>A
NG_009060.1:g.29126G>A
LRG_274:g.29126G>A
LRG_274t1:c.1359-29G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000019.10:11113505:G:A

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.

The Genome Aggregation Database (gnomAD), exomes 0.00000

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA10585421 LDLR-LOVD, British Heart Foundation: LDLR_001407 dbSNP: rs879254877 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	4580	4921
MIR6886	-	-	-	GRCh38	-	62

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 benign (1)	criteria provided, single submitter	Mar 25, 2016	RCV000237721.1
Familial hypercholesterolemia	Likely benign (1)	criteria provided, single submitter	Dec 1, 2020	RCV001526180.2
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	Aug 7, 2024	RCV004992123.1

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.	Expand all rows Collapse all rows 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 benign (Mar 25, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACGS Guidelines, 2013)	Familial hypercholesterolemia	LDLR-LOVD, British Heart Foundation Accession: SCV000295388.2 First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016	Publications: PubMed (1) PubMed: 20809525 Observation: 1 Collection method: literature only Allele origin: germline Affected status: yes more Observation 1 Collection method: literature only Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Likely benign (Dec 01, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Familial hypercholesterolemia	Color Diagnostics, LLC DBA Color Health Accession: SCV001736481.1 First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS

Likely benign (Aug 07, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV005609309.1 First in ClinVar: Jan 13, 2025 Last updated: Jan 13, 2025	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Molecular spectrum of autosomal dominant hypercholesterolemia in France.	Marduel M	Human mutation	2010	PMID: 20809525

Text-mined citations for rs879254877 ...

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 Apr 13, 2026