ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1951G>A (p.Asp651Asn) (rs730882110)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238255 SCV000503436 likely pathogenic Familial hypercholesterolemia 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 , family members = 3 with co-segregation / previously described in association with FH/Software predictions: Conflicting
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162005 SCV000189580 not provided not provided no assertion provided in vitro
Fundacion Hipercolesterolemia Familiar RCV000238255 SCV000607657 uncertain significance Familial hypercholesterolemia 2016-03-01 criteria provided, single submitter research
Integrated Genetics/Laboratory Corporation of America RCV000590648 SCV000697217 likely pathogenic Familial hypercholesterolemias 2016-05-19 criteria provided, single submitter clinical testing Variant summary: The LDLR c.1951G>A (p.Asp651Asn) variant involves the alteration of a conserved nucleotide and is located in 'precursor homology' domain. 3/4 in silico tools predict a damaging outcome (SNPs&GO not captured due to low reliability index). This variant was found in 1/131578 control chromosomes at a frequency of 0.0000076, which does not exceed the estimated maximal expected allele frequency of a pathogenic LDLR variant (0.0012508). This variant has been found in three apparently non-related FH patients (Mozas_2004) as well as in one patient with myocardial infarction (Do_2015). Other missense changes at this codon such as Asp651Tyr has also been detected in FH patients, suggesting that the codon may be a mutational hot-spot. Taken together, it variant has been classified as a Probable Disease Variant (or likely pathogenic).
LDLR-LOVD, British Heart Foundation RCV000238255 SCV000295769 uncertain significance Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000238255 SCV000540849 likely pathogenic Familial hypercholesterolemia 2016-11-05 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.