Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237744 | SCV000294453 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237744 | SCV000503099 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 2 , family member = 1 with co-segregation |
U4M - |
RCV000237744 | SCV000583626 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | ACMG Guidelines: Likely Pathogenic (ii) |
Fundacion Hipercolesterolemia Familiar | RCV000237744 | SCV000607411 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Color Diagnostics, |
RCV000775250 | SCV000909508 | pathogenic | Familial hypercholesterolemia | 2018-08-20 | criteria provided, single submitter | clinical testing | Pathogenic variant based on current evidence: This variant changes a single nucleotide in exon 2 of the LDLR gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Loss-of-function truncation variants in the LDLR gene are known to be pathogenic (PMID: 20809525). Based on available evidence, this variant is classified as Pathogenic. |
Labcorp Genetics |
RCV000775250 | SCV001587271 | pathogenic | Familial hypercholesterolemia | 2023-03-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 251009). This variant is also known as C6X. This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 15556094, 23375686). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys27*) 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). |
Ambry Genetics | RCV002429161 | SCV002680118 | pathogenic | Cardiovascular phenotype | 2024-08-08 | criteria provided, single submitter | clinical testing | The p.C27* pathogenic mutation (also known as c.81C>A), located in coding exon 2 of the LDLR gene, results from a C to A substitution at nucleotide position 81. This changes the amino acid from a cysteine to a stop codon within coding exon 2. This alteration (also referred to as p.C6*) has been reported in hypercholesterolemia cohorts (Laurie AD et al. Atheroscler Suppl, 2004 Dec;5:13-5; Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8). 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. |