Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000821415 | SCV000962170 | pathogenic | Neurofibromatosis, type 1 | 2023-09-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 663523). Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in exon 32 (PMID: 23913538). This variant disrupts a region of the NF1 protein in which other variant(s) (p.Leu1425Pro) have been determined to be pathogenic (PMID: 10607834, 10712197, 31730495). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 18800150, 23913538). This sequence change affects an acceptor splice site in intron 31 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). |