Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237585 | SCV000295653 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
U4M - |
RCV000237585 | SCV000494601 | pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237585 | SCV000503414 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 / previously described in association with FH/software prediction damaging |
Laboratory of Genetics and Molecular Cardiology, |
RCV000237585 | SCV000588606 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Fundacion Hipercolesterolemia Familiar | RCV000237585 | SCV000607640 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Athena Diagnostics Inc | RCV000518174 | SCV000614004 | likely pathogenic | not provided | 2017-06-16 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000588105 | SCV000697210 | pathogenic | Familial hypercholesterolemia | 2019-09-30 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.1783C>T (p.Arg595Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251488 control chromosomes. c.1783C>T has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia in the homozygous and compound heterozygous state (Mozas_2004, Junyent_2010, Damgaard_2005, Chiou_2012, Pek_2018, Pirillo_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments, three as VUS, six as likely pathogenic/pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Iberoamerican FH Network | RCV000237585 | SCV000748099 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Invitae | RCV000588105 | SCV000752411 | pathogenic | Familial hypercholesterolemia | 2019-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 595 of the LDLR protein (p.Arg595Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs373371572, ExAC 0.001%). This variant has been observed in several individuals affected with familial hypercholesterolaemia (PMID: 11737238, 25461735, 27784735, 16250003, 20538126). ClinVar contains an entry for this variant (Variation ID: 161290). This variant disrupts the p.Arg595 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 15359125, 15256764, 16250003, 18718593, 25437892, 25487149, 27497240, 28502510), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |
Color | RCV000588105 | SCV000909180 | likely pathogenic | Familial hypercholesterolemia | 2019-03-22 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000237585 | SCV001149823 | likely pathogenic | Familial hypercholesterolemia 1 | 2018-12-27 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000518174 | SCV001433287 | likely pathogenic | not provided | 2020-03-16 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000237585 | SCV001440210 | uncertain significance | Familial hypercholesterolemia 1 | 2019-01-01 | criteria provided, single submitter | clinical testing | |
CSER _CC_NCGL, |
RCV000148597 | SCV000190312 | uncertain significance | Hypercholesterolaemia | 2014-06-01 | no assertion criteria provided | research | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237585 | SCV000606512 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research |