Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000806711 | SCV000946725 | pathogenic | Neurofibromatosis, type 1 | 2023-04-27 | criteria provided, single submitter | clinical testing | 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: 651367). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 15060124; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 43 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). |
Ce |
RCV001092513 | SCV001249054 | likely pathogenic | not provided | 2019-10-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000806711 | SCV002560204 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001092513 | SCV003930885 | pathogenic | not provided | 2023-06-12 | 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); This variant is associated with the following publications: (PMID: 15060124) |
Ambry Genetics | RCV004559681 | SCV005048667 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-05-03 | criteria provided, single submitter | clinical testing | The c.6641+1delG intronic pathogenic mutation, located in intron 43 of the NF1 gene, results from a deletion of one nucleotide within intron 43 of the NF1 gene. This alteration has been reported in an individual with a clinical diagnosis of neurofibromatosis type 1 (Mattocks C et al. J Med Genet, 2004 Apr;41:e48). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |