Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000462352 | SCV000541982 | likely pathogenic | Neurofibromatosis, type 1 | 2022-12-14 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 and/or neurofibromatosis type 1 (PMID: 12807981; Invitae). ClinVar contains an entry for this variant (Variation ID: 404430). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.1260+5G nucleotide in the NF1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 25074460, 29483232; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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. |
Juno Genomics, |
RCV000462352 | SCV005415719 | likely pathogenic | Neurofibromatosis, type 1 | criteria provided, single submitter | clinical testing | PM2_Supporting+PS3+PM6_Supporting+PP4 |