Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Robarts Research Institute, |
RCV000408847 | SCV000484808 | likely pathogenic | Hypercholesterolemia, familial, 1 | criteria provided, single submitter | clinical testing | ||
| Fundacion Hipercolesterolemia Familiar | RCV000408847 | SCV000607652 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Gene |
RCV001731662 | SCV001982811 | pathogenic | not provided | 2021-04-09 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies show that expression of LDLR is significantly diminished in vitro (Banerjee et al., 2019); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#369872; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 19026292, 31578082) |
| Labcorp Genetics |
RCV001861359 | SCV002232528 | pathogenic | Familial hypercholesterolemia | 2022-05-28 | 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: 369872). This variant is also known as 1877delA. This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 19026292). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala627Profs*38) 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 | RCV002411271 | SCV002722382 | pathogenic | Cardiovascular phenotype | 2017-09-14 | criteria provided, single submitter | clinical testing | The c.1878delA pathogenic mutation, located in coding exon 13 of the LDLR gene, results from a deletion of one nucleotide at nucleotide position 1878, causing a translational frameshift with a predicted alternate stop codon (p.A627Pfs*38). This alteration (reported as 1877delA) was detected in a patient reported to have homozygous familial hypercholesterolemia (Kolansky DM et al. Am J Cardiol. 2008;102:1438-43). 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. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000408847 | SCV000606549 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |