Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000532988 | SCV000628567 | pathogenic | Neurofibromatosis, type 1 | 2024-09-10 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 30 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 individual(s) with neurofibromatosis type 1 (PMID: 9003501, 10712197). ClinVar contains an entry for this variant (Variation ID: 457679). 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. |
| Ambry Genetics | RCV002316505 | SCV000670509 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2016-11-16 | criteria provided, single submitter | clinical testing | The c.4110+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 30 of the NF1 gene. This mutation was identified in 1/320 unrelated patients diagnosed with neurofibromatosis type 1 (NF1), and the proband carrying this mutation also had a family history of NF1 (Upadhyaya M et al. Hum. Genet., 1997 Jan;99:88-92). In addition to the clinical data presented in the literature, 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 a disease-causing mutation. |
| Genome- |
RCV000532988 | SCV002560024 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV003480669 | SCV004224650 | likely pathogenic | not provided | 2022-03-08 | criteria provided, single submitter | clinical testing | PM2_very_strong, PVS1_moderate |
| Institute of Human Genetics, |
RCV000532988 | SCV004229060 | pathogenic | Neurofibromatosis, type 1 | 2023-12-29 | criteria provided, single submitter | clinical testing |