Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001246803 | SCV001420188 | pathogenic | Familial hypercholesterolemia | 2019-07-17 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with LDLR-related conditions. This sequence change creates a premature translational stop signal (p.Asp221Ilefs*8) in the LDLR gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002366084 | SCV002663161 | pathogenic | Cardiovascular phenotype | 2020-12-24 | criteria provided, single submitter | clinical testing | The c.661delGinsATCAC pathogenic mutation, located in coding exon 4 of the LDLR gene, results from the deletion of one nucleotide and insertion of 5 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.D221Ifs*8). 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. |