Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000003886 | SCV000295560 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Robarts Research Institute, |
RCV000003886 | SCV000484682 | likely pathogenic | Familial hypercholesterolemia 1 | criteria provided, single submitter | clinical testing | ||
Centre de Génétique Moléculaire et Chromosomique, |
RCV000003886 | SCV000503381 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 4 , family member = 1 with co-segregation / FH-Palermo, 2% LDLR activity / Software predictions: Damaging |
Molecular Genetics Laboratory, |
RCV000003886 | SCV000540828 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000587938 | SCV000544685 | pathogenic | Familial hypercholesterolemia | 2019-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with aspartic acid at codon 549 of the LDLR protein (p.Gly549Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs28941776, ExAC 0.009%). This variant is clearly defined as a familial hypercholesterolemia causative allele (PMID: 23375686, 25487149). It is a common cause of familial hypercholesterolemia in individuals of Italian ancestry. This variant is also known as p.Glu528Asp in the literature. ClinVar contains an entry for this variant (Variation ID: 3698). Experimental studies have shown that this missense change inhibits the transport of the LDLR protein to the cellular surface (PMID: 25647241). For these reasons, this variant has been classified as Pathogenic. |
U4M - |
RCV000003886 | SCV000583858 | pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Laboratory of Genetics and Molecular Cardiology, |
RCV000003886 | SCV000588600 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Fundacion Hipercolesterolemia Familiar | RCV000003886 | SCV000607619 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Integrated Genetics/Laboratory Corporation of America | RCV000587938 | SCV000697207 | pathogenic | Familial hypercholesterolemia | 2017-03-17 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000003886 | SCV000894176 | pathogenic | Familial hypercholesterolemia 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Color | RCV000587938 | SCV001346737 | pathogenic | Familial hypercholesterolemia | 2017-07-19 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000003886 | SCV001433282 | pathogenic | Familial hypercholesterolemia 1 | 2020-02-11 | criteria provided, single submitter | clinical testing | |
Human Genome Sequencing Center Clinical Lab, |
RCV000587938 | SCV001435010 | pathogenic | Familial hypercholesterolemia | 2018-08-06 | criteria provided, single submitter | clinical testing | The c.1646G>A (p.Gly549Asp) variant has been reported in multiple unrelated patients with familial hypercholesterolemia (PMID 1301956,9259195, 9544850, 11810272, 15199436, 15241806, 19837725, 21865347, 23375686) or myocardial infarction (PMID 25487149). A functional study reported the mutant LDLR protein retains less than 2 percent receptor activity compared to wild type LDLR protein (PMID 1301956) and the variant is classified as 'disruptive' through systematic cell-based phenotyping (PMID 25647241). Therefore, this c.1646G>A (p.Gly549Asp) variant is classified as pathogenic. |
OMIM | RCV000003886 | SCV000024051 | pathogenic | Familial hypercholesterolemia 1 | 1988-11-01 | no assertion criteria provided | literature only | |
Dept. |
RCV000161997 | SCV000189572 | not provided | not provided | no assertion provided | in vitro | ||
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000003886 | SCV000606474 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research | ||
Diagnostic Laboratory, |
RCV000003886 | SCV000733824 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | clinical testing | ||
Iberoamerican FH Network | RCV000003886 | SCV000748175 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | no assertion criteria provided | research |