Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000238474 | SCV000295546 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | research | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000238474 | SCV000503378 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 3(1 compound heterozygote) , family members = 2 with co-segregation/Software predictions: Conflicting |
Molecular Genetics Laboratory, |
RCV000238474 | SCV000540831 | pathogenic | Familial hypercholesterolemia 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
U4M - |
RCV000238474 | SCV000583856 | pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001321570 | SCV001512406 | uncertain significance | Familial hypercholesterolemia | 2020-07-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 545 of the LDLR protein (p.Gly545Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 20809525, 26343872, Invitae). ClinVar contains an entry for this variant (Variation ID: 251942). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). This variant disrupts the p.Gly545 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 23535506, 26020417), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238474 | SCV000606471 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research |