Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000806570 | SCV000946574 | pathogenic | Neurofibromatosis, type 1 | 2018-11-01 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 14-57 of the NF1 gene. The 5' boundary is likely confined to intron 13. 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. A similar deletion of exons 14-57 has been reported in an individual affected with neurofibromatosis, type1 (PMID: 25631097). This variant has also been reported as a deletion of exons 14-58. Multiple missense variants, including p.Arg1809Cys, p.Arg1809Leu, and p.Phe1863Leu, located within the deleted region, have been determined to be pathogenic (PMID: 24357598, 25966637, 22190595). In addition, a, sub-genic deletion of exons of 36-57 (also reported as a deletion of exons 28-49) has been determined to be pathogenic (PMID: 24232412, 16283621). Therefore, deletions that fully encompass this region are also expected to be pathogenic. For these reasons, this variant has been classified as Pathogenic. |