Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000497054 | SCV000829850 | pathogenic | Neurofibromatosis, type 1 | 2022-06-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 431613). Disruption of this splice site has been observed in individuals with neurofibromatosis type-1 (PMID: 17311297; Invitae). This sequence change affects a donor splice site in intron 22 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). |
Gene |
RCV002289682 | SCV002578407 | likely pathogenic | not provided | 2022-04-06 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as IVS17+1G>A; This variant is associated with the following publications: (PMID: 17311297) |
Ambry Genetics | RCV002438206 | SCV002746907 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-08-20 | criteria provided, single submitter | clinical testing | The c.2990+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 22 of the NF1 gene. The mutation has been identified in individuals with a clinical diagnosis or suspicion of neurofibromatosis type 1 (Wimmer K et al. Hum Mutat, 2007 Jun;28:599-612; Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing (Wimmer K et al. Hum Mutat, 2007 Jun;28:599-612; Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Medical Genetics, |
RCV000497054 | SCV000588752 | likely pathogenic | Neurofibromatosis, type 1 | 2017-02-02 | no assertion criteria provided | clinical testing |