Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590309 | SCV000696659 | uncertain significance | not provided | 2017-02-20 | criteria provided, single submitter | clinical testing | Variant summary: The APOB c.10848delT (p.Gly3617Alafs) variant results in a premature termination codon, predicted to cause a truncated or absent APOB protein due to nonsense mediated decay. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121178 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. However, there is no evidence regarding the impact of a dosage reduction in apo-B-100 (due to this frameshift) on the ability of LDL to bind its receptors. Taken together, this variant is classified as VUS until additional evidence becomes available. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV001814190 | SCV002061665 | pathogenic | Familial hypobetalipoproteinemia 1 | 2021-10-26 | criteria provided, single submitter | clinical testing | PVS1, PM2_Supporting, PS3_Moderate, PS4_Moderate |
| Genetic Services Laboratory, |
RCV000590309 | SCV002067281 | pathogenic | not provided | 2019-03-27 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the APOB gene demonstrated a single base pair deletion in exon 26, c.10848del. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 5 amino acids downstream of the mutation, p.Gly3617Alafs*6. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated APOB protein with potentially abnormal function. This pathogenic sequence change has not been previously been described in patients with APOB-related disorders, however, truncating sequence changes are reported and are mainly associated with autosomal recessive hypobetalipoproteinemia (PMID: 24288038). |
| Invitae | RCV003767336 | SCV004603496 | pathogenic | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2023-07-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly3617Alafs*6) in the APOB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APOB are known to be pathogenic (PMID: 20032471). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with familial hypobetalipoproteinemia (PMID: 29572815, 33207932). ClinVar contains an entry for this variant (Variation ID: 495857). For these reasons, this variant has been classified as Pathogenic. |