Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000474467 | SCV000542018 | uncertain significance | Neurofibromatosis, type 1 | 2023-09-14 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 3 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 (PMID: 31370276). ClinVar contains an entry for this variant (Variation ID: 404451). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Gene |
RCV001550211 | SCV001770507 | likely pathogenic | not provided | 2020-10-19 | criteria provided, single submitter | clinical testing | Published functional studies report this variant results in an in-frame deletion of 28 amino acids in a non-repeat region (Giugliano 2019); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 31370276) |
Athena Diagnostics | RCV001550211 | SCV001879391 | pathogenic | not provided | 2021-02-17 | criteria provided, single submitter | clinical testing | Assessment of experimental evidence suggests this variant will result in the removal of a section of the protein due to abnormal RNA splicing (PMID: 31370276). This variant has been identified in at least one individual with clinical features associated with this gene. Several other splice variants at this junction are reported to be pathogenic or likely pathogenic. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). |
Medical Genetics, |
RCV000474467 | SCV002567795 | likely pathogenic | Neurofibromatosis, type 1 | 2022-08-17 | criteria provided, single submitter | clinical testing |