Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001386872 | SCV001587263 | pathogenic | Neurofibromatosis, type 1 | 2022-12-13 | 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. Studies have shown that disruption of this splice site results in skipping of exon 30 (also known as 23.2) and introduces a premature termination codon (PMID: 10712197). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 1073774). Disruption of this splice site has been observed in individuals with clinical features of neurofibromatosis type 1 (PMID: 16944272, 25074460; Invitae). This sequence change affects an acceptor splice site in intron 29 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. |
Ambry Genetics | RCV002377575 | SCV002624566 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-04-26 | criteria provided, single submitter | clinical testing | The c.3975-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 30 of the NF1 gene. This alteration was reported in an individual with a clinical diagnosis of neurofibromatosis type 1 (Pasmant E et al. Eur J Hum Genet. 2015 May;23:596-601). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. 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. |