Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000707960 | SCV000837070 | pathogenic | Neurofibromatosis, type 1 | 2019-02-28 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 36-57 of the NF1 gene. The 5' boundary is likely confined to intron 35. 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. Similar deletions of exons 36-57 have been observed in individuals affected with neurofibromatosis type 1 (Invitae). Multiple missense variants, including p.Arg1809Cys, p.Arg1809Leu, and p.Arg1849Gln, located within the deleted region, have been determined to be pathogenic (PMID: 10607834, 10980545, 24357598, 12807981, 26178382). This suggests that this region is critical for NF1 protein function and that the deletion of this larger portion of the NF1 protein may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. |