Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001379109 | SCV001576845 | likely pathogenic | not provided | 2018-05-29 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 17-37 of the IKBKAP gene. The 5' boundary is likely confined to intron 16. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with IKBKAP-related disease. The p.Arg696Pro amino acid residue in IKBKAP has been determined to be clinically significant (PMID: 11179008, 11179021, 12116234, 11179021). This suggests that variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Invitae | RCV000708157 | SCV000837267 | likely pathogenic | Familial dysautonomia | 2018-06-05 | flagged submission | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 17-37 of the IKBKAP gene. The 5' boundary is likely confined to intron 16. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with IKBKAP-related disease. The p.Arg696Pro amino acid residue in IKBKAP has been determined to be clinically significant (PMID: 11179008, 11179021, 12116234, 11179021). This suggests that variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |