Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000460682 | SCV000542165 | pathogenic | Neurofibromatosis, type 1 | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 13 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: 17311297; Invitae). ClinVar contains an entry for this variant (Variation ID: 404566). 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. For these reasons, this variant has been classified as Pathogenic. |
Center for Human Genetics, |
RCV000460682 | SCV000781912 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000460682 | SCV001479090 | uncertain significance | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001753864 | SCV002007399 | likely pathogenic | not provided | 2021-07-21 | criteria provided, single submitter | clinical testing | Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 31766501, 17311297) |
Ambry Genetics | RCV002393082 | SCV002705166 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-01-27 | criteria provided, single submitter | clinical testing | The c.1527+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 13 in the NF1 gene. This nucleotide position is highly conserved in available vertebrate species. This variant was detected in multiple individuals with features of or clinical diagnosis of neurofibromatosis type 1 (Melloni G et al. Cancers (Basel), 2019 11;11:; personal communication with GeneDx, Invitae, and the Hospital for Sick Children). In silico splice site analysis predicts that this alteration may weaken the native splice donor site. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |