Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001964732 | SCV002200784 | pathogenic | Neurofibromatosis, type 1 | 2023-04-26 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NF1 protein in which other variant(s) (p.Arg1066Thr; p.Trp1048Arg) have been determined to be pathogenic (PMID: 23758643; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Studies have shown that disruption of this splice site results in skipping of exon 24 (referred to as exon19a), but is expected to preserve the integrity of the reading-frame (PMID: 10607834). ClinVar contains an entry for this variant (Variation ID: 1427919). Disruption of this splice site has been observed in individual(s) with clinical features of neurofibromatosis, type 1 and/or neurofibromatosis type 1 (PMID: 10607834, 18546366). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 24 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. |