Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237793 | SCV000294417 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237793 | SCV000503092 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1, family members =2 with co-segregation / software predictions: conflicting |
U4M - |
RCV000237793 | SCV000583623 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | ACMG Guidelines: Likely Pathogenic (ii) |
Laboratory of Genetics and Molecular Cardiology, |
RCV000237793 | SCV000588480 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002436068 | SCV002751844 | likely pathogenic | Cardiovascular phenotype | 2019-04-30 | criteria provided, single submitter | clinical testing | The p.W10R variant (also known as c.28T>C), located in coding exon 1 of the LDLR gene, results from a T to C substitution at nucleotide position 28. The tryptophan at codon 10 is replaced by arginine, an amino acid with dissimilar properties. This variant has been described in familial hypercholesterolemia (FH) cohorts, although clinical details were limited (Fouchier SW et al. Hum. Mutat., 2005 Dec;26:550-6; Jannes CE et al. Atherosclerosis, 2015 Jan;238:101-7). An alternate nucleotide change at this position, p.W10R c.28T>A, was reported to be de novo in a pediatric FH case, and functional activity in skin fibroblasts showed reduced LDLR activity (Cassanelli S et al. Clin. Genet., 1998 May;53:391-5). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Labcorp Genetics |
RCV005090198 | SCV005837000 | pathogenic | Familial hypercholesterolemia | 2024-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 10 of the LDLR protein (p.Trp10Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 9660059, 16250003, 25461735; internal data). In at least one individual the variant was observed to be de novo. This variant is also known as W12R. ClinVar contains an entry for this variant (Variation ID: 250976). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LDLR protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237793 | SCV000605997 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
Diagnostic Laboratory, |
RCV000237793 | SCV000733809 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV001699170 | SCV001920172 | likely pathogenic | not provided | no assertion criteria provided | clinical testing |