Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000527.5(LDLR):c.2206G>A (p.Val736Ile)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Jul 16, 2021)
Last evaluated:
May 1, 2020
Accession:
VCV000375835.5
Variation ID:
375835
Description:
single nucleotide variant
Help

NM_000527.5(LDLR):c.2206G>A (p.Val736Ile)

Allele ID
362727
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
19p13.2
Genomic location
19: 11123239 (GRCh38) GRCh38 UCSC
19: 11233915 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_274:g.38859G>A
LRG_274t1:c.2206G>A LRG_274p1:p.Val736Ile
NM_000527.4:c.2206G>A NP_000518.1:p.Val736Ile missense
... more HGVS
Protein change
V736I, V568I, V558I, V695I
Other names
-
Canonical SPDI
NC_000019.10:11123238:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Links
ClinGen: CA039136
dbSNP: rs547268730
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 criteria provided, single submitter Dec 16, 2016 RCV000417287.2
Uncertain significance 1 criteria provided, single submitter Mar 20, 2020 RCV000775613.2
Uncertain significance 1 criteria provided, single submitter Feb 6, 2019 RCV001192515.1
Uncertain significance 1 criteria provided, single submitter May 1, 2020 RCV001536350.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
LDLR Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3093 3293

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Dec 16, 2016)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia 1
Allele origin: germline
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
Accession: SCV000503473.1
Submitted: (Jan 23, 2017)
Evidence details
Comment:
subject mutated among 2600 FH index cases screened = 1/Software predictions: Benign
Uncertain significance
(Mar 20, 2020)
criteria provided, single submitter
Method: clinical testing
Familial hypercholesterolemia
Allele origin: germline
Color Health, Inc
Accession: SCV000909977.2
Submitted: (May 19, 2020)
Comment:
This missense variant (also known as p.Val715Ile in the mature protein) replaces valine with isoleucine at codon 736 of the LDLR protein. Computational prediction suggests … (more)
Evidence details
Uncertain significance
(Feb 06, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001360709.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Variant summary: The variant, LDLR c.2206G>A (p.Val736Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict … (more)
Uncertain significance
(May 01, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001753093.1
Submitted: (Jul 16, 2021)
Evidence details
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar with conflicting interpretations of pathogenicity (ClinVar Variant ID#375835; … (more)
Pathogenic
(-)
no assertion criteria provided
Method: research
Familial hypercholesterolemia
Allele origin: germline
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum
Accession: SCV000606615.1
Submitted: (Apr 25, 2017)
Evidence details

Functional evidence

Help
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 this variant

Help
Title Author Journal Year Link
Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia - a proof-of-concept study. Maurer F Swiss medical weekly 2016 PMID: 27497240

Text-mined citations for rs547268730...

Help
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 Oct 24, 2021