Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237398 | SCV000294734 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Centre de Génétique Moléculaire et Chromosomique, |
RCV000237398 | SCV000503166 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 , family member = 1 with co-segregation / Software predictions: Damaging |
| U4M - |
RCV000237398 | SCV000583684 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002284384 | SCV002574406 | likely pathogenic | not provided | 2022-03-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as C139R; This variant is associated with the following publications: (PMID: 32331935, 12417285, 12436241, 16389549, 31491741, 34848321) |
| Ambry Genetics | RCV002327176 | SCV002634372 | pathogenic | Cardiovascular phenotype | 2020-03-31 | criteria provided, single submitter | clinical testing | The p.C160R pathogenic mutation (also known as c.478T>C), located in coding exon 4 of the LDLR gene, results from a T to C substitution at nucleotide position 478. The cysteine at codon 160, located in LDLR class A repeat 4, is replaced by arginine, an amino acid with highly dissimilar properties. Pathogenic LDLR mutations that result in the substitution or generation of cysteine residues within the cysteine-rich LDLR class A repeats and EGF-like domains are common in familial hypercholesterolemia (FH) (Villéger L. Hum Mutat. 2002;20(2):81-7). This particular cysteine change, also referred to as C139R, has been detected in individuals from various FH cohorts (Amsellem S et al. Hum. Genet., 2002 Dec;111:501-10; Yu W et al. Atherosclerosis, 2002 Dec;165:335-42; Humphries SE et al. J. Mol. Med., 2006 Mar;84:203-14). Other variants affecting this codon (p.C160Y, p.C160G, and p.C160F) have also been detected in FH cohorts (Day IN et al. Hum. Mutat., 1997;10:116-27; Chakir Kh et al. Mol. Genet. Metab., 1998 Jan;63:31-4; Bourbon M et al. Atherosclerosis, 2017 07;262:8-13). Internal structural analysis indicates this alteration eliminates a disulfide bond critical for the structural integrity of LDLR class A repeat 4 (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237398 | SCV000606131 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |