Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001390890 | SCV001592756 | pathogenic | Familial hypercholesterolemia | 2020-06-06 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with clinical features of familial hypercholesterolemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 440700). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the LDLR protein. Other variant(s) that disrupt this region (p.Ser849*) have been determined to be pathogenic (PMID: 26892515, 11933210, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the LDLR gene (p.Asp834Metfs*95). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acids of the LDLR protein and extend the protein by an additional 67 amino acids. |
| Ambry Genetics | RCV004023447 | SCV005035838 | uncertain significance | Cardiovascular phenotype | 2024-01-31 | criteria provided, single submitter | clinical testing | The c.2500delG variant, located in coding exon 17 of the LDLR gene, results from a deletion of one nucleotide at nucleotide position 2500, causing a translational frameshift with a predicted alternate stop codon (p.D834Mfs*95). This alteration occurs at the 3' terminus of theLDLR gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 3% of the protein. The exact functional effect of this alteration is unknown. This alteration has been reported in a hypercholesterolemia cohort; however, clinical details were limited (Leren TP et al. Atherosclerosis, 2021 Apr;322:61-66). Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000508927 | SCV000606663 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |