Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Medical Genomics Laboratory, |
RCV001007741 | SCV001167416 | pathogenic | Neurofibromatosis, type 1 | 2020-01-20 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV001007741 | SCV001250660 | pathogenic | Neurofibromatosis, type 1 | 2020-01-20 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001007741 | SCV001408079 | likely pathogenic | Neurofibromatosis, type 1 | 2022-10-25 | criteria provided, single submitter | clinical testing | 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. Studies have shown that this variant results in the activation of a cryptic splice site in intron 14 (PMID: 27074763, 32126153). ClinVar contains an entry for this variant (Variation ID: 816755). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 27074763; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 14 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the gain of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. |