Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237235 | SCV000295073 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Cardiovascular Research Group, |
RCV000237235 | SCV000322920 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | 0/190 non-FH alleles |
Molecular Genetics Laboratory, |
RCV000237235 | SCV000540772 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
U4M - |
RCV000237235 | SCV000583764 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000775228 | SCV000909479 | pathogenic | Familial hypercholesterolemia | 2018-03-23 | criteria provided, single submitter | clinical testing | Pathogenic variant based on current evidence: This variant (also known as C292X and FH-Cyprus) changes one nucleotide in exon 6 of the LDLR gene. This creates a premature translational stop signal and is expected to result in an absent or non-functional protein product. Truncating variants in LDLR are known to be pathogenic (PMID: 20809525). While this variant is rare in the general population (0/277264 chromosomes in the Genome Aggregation Database (gnomAD)), it has been reported in multiple individuals affected with familial hypercholesterolemia (PMID: 1301956, 17142622, 21310417, 22698793). Based on available evidence, this variant is classified as Pathogenic. |
Brunham Lab, |
RCV000237235 | SCV001432673 | pathogenic | Hypercholesterolemia, familial, 1 | 2019-06-04 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002446475 | SCV002682440 | pathogenic | Cardiovascular phenotype | 2022-08-29 | criteria provided, single submitter | clinical testing | The p.C313* pathogenic mutation (also known as c.939C>A), located in coding exon 6 of the LDLR gene, results from a C to A substitution at nucleotide position 939. This changes the amino acid from a cysteine to a stop codon within coding exon 6. This variant (also referred to as p.C292* and FH Cyprus) has been detected in individuals from numerous familial hypercholesterolemia (FH) cohorts of various ethnic backgrounds, including a homozygous occurrence and co-occurrence with a PCSK9 variant in individuals with features consistent with homozygous FH (Leren TP et al. Atherosclerosis, 2021 04;322:61-66; Hori M et al. Atherosclerosis, 2019 10;289:101-108; Saracoglu E et al. Echocardiography, 2018 09;35:1289-1299; Tichý L et al. Atherosclerosis, 2012 Aug;223:401-8; Noguchi T et al. Atherosclerosis, 2010 May;210:166-72; Glynou K et al. Clin Biochem, 2008 Mar;41:335-42; Humphries SE et al. J Med Genet, 2006 Dec;43:943-9; Xenophontos SL et al. Hum Mutat, 2000 Apr;15:380; Webb JC et al. J Lipid Res, 1996 Feb;37:368-81). Assays performed on patient cells homozygous for this variant indicated significantly reduced LDL-R activity (Webb JC et al. J Lipid Res, 1996 Feb;37:368-81). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Revvity Omics, |
RCV000237235 | SCV003819498 | pathogenic | Hypercholesterolemia, familial, 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000775228 | SCV004298339 | pathogenic | Familial hypercholesterolemia | 2023-08-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys313*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 251539). This variant is also known as FH Cyprus, Cys292Ter, and C292X. This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 1301956, 10737984, 30241732, 31491741). This variant is not present in population databases (gnomAD no frequency). |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237235 | SCV000606275 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |