Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000702952 | SCV000831829 | pathogenic | Neurofibromatosis, type 1 | 2023-10-09 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 16 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. 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: 9195229, 11292340). This variant is also known as c.2056+1G>A. ClinVar contains an entry for this variant (Variation ID: 579615). Studies have shown that disruption of this splice site results in skipping of exons 15-16, but is expected to preserve the integrity of the reading-frame (PMID: 11292340). This variant disrupts the p.His553 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16944272, 27322474, 27838393). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001552526 | SCV001773228 | pathogenic | not provided | 2023-11-08 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: Canonical splice variant shown to result in an in-frame deletion of exons 15 and 16, reported as exons 11 and 12a in the literature (PMID: 11292340); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29680930, 25525159, 23913538, 10712197, 9195229, 25486365, 11292340, 34418705, 31533651) |
Hudson |
RCV000702952 | SCV001787147 | pathogenic | Neurofibromatosis, type 1 | 2021-07-22 | criteria provided, single submitter | research | ACMG codes: PVS1; PM2; PP5 |
Genome- |
RCV000702952 | SCV002561713 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004559629 | SCV005048574 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-04-27 | criteria provided, single submitter | clinical testing | The c.1845+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 16 of the NF1 gene. This alteration was detected in individuals with neurofibromatosis type 1 (NF1) (Fang LJ et al. J Mol Biol, 2001 Apr;307:1261-70; Chai P et al. BMC Med Genet, 2019 Sep;20:158). This nucleotide position is highly conserved in available vertebrate species. 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 in the set of samples tested (Fang LJ et al. J Mol Biol, 2001 Apr;307:1261-70; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Baylor Genetics | RCV004569373 | SCV005052348 | pathogenic | Juvenile myelomonocytic leukemia | 2023-11-08 | criteria provided, single submitter | clinical testing |