Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000681123 | SCV000808581 | pathogenic | not provided | 2021-10-05 | 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 (Lek 2016); This variant is associated with the following publications: (PMID: 23010473, 10543400) |
| Labcorp Genetics |
RCV001861892 | SCV002148397 | pathogenic | Neurofibromatosis, type 1 | 2022-08-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 15 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 17311297, 29685074; Invitae). ClinVar contains an entry for this variant (Variation ID: 561743). 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. |
| Genome- |
RCV001861892 | SCV002561701 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002397356 | SCV002714196 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-03-19 | criteria provided, single submitter | clinical testing | The c.1722-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 16 of the NF1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. 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. As such, this alteration is classified as likely pathogenic. |