Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000213933 | SCV000271426 | pathogenic | Neurofibromatosis, type 1 | 2016-03-28 | criteria provided, single submitter | clinical testing | The p.Tyr2285X variant in NF1 has been reported in >10 individuals with Neurofib romatosis I (NF1) (Upadhyaya 1996, Leiden Open Variation Database), 3 of which w ere apparently de novo. It was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This nonsen se variant leads to a premature termination codon at position 2285, which is pre dicted to lead to a truncated or absent protein. Heterozygous loss-of-function o f the NF1 gene is an established disease mechanism in NF1. In summary, this vari ant meets our criteria to be classified as pathogenic for NF1 in an autosomal do minant manner. |
| Gene |
RCV000486063 | SCV000568612 | pathogenic | not provided | 2018-05-23 | criteria provided, single submitter | clinical testing | The c.6791dupA variant in the NF1 gene has been reported previously in association with neurofibromatosis, type 1 (Upadhyaya et al., 1996; De Luca et al., 2004; Maruoka et al., 2014). Note that alternate nomenclature c.6853_6854insA was used by Maruoka et al. (2014). The c.6791dupA causes a frameshift, changing codon Tyrosine 2264 to a premature Stop codon, denoted p.Tyr2264Ter. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.6791dupA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.6791dupA as a pathogenic variant. |
| Invitae | RCV000213933 | SCV000816867 | pathogenic | Neurofibromatosis, type 1 | 2019-12-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr2264*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with neurofibromatosis type 1 (PMID: 25325900, 8837715, 24232412, 16941471, 27838393, 17311297, 23913538). This variant is also known as p.Tyr2285* in the literature. ClinVar contains an entry for this variant (Variation ID: 228382). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic. |
| The Laboratory of Genetics and Metabolism, |
RCV001009583 | SCV001169684 | pathogenic | Neurofibromatosis, type 1; Tibial pseudoarthrosis | 2018-11-10 | criteria provided, single submitter | research |