Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV001591637 | SCV001815651 | pathogenic | Neurofibromatosis, type 1; Café-au-lait macules with pulmonary stenosis | 2020-09-23 | criteria provided, single submitter | clinical testing | The inherited heterozygous variant (c.1882del, p.Tyr628ThrfsTer3) has been reported in individuals affected with NF1-related disorders [PMID: 24789688; PMID: 30530636]. The variant is absent from gnomAD(v3) database indicating it is an extremely rare allele in the populations represented in this database. This one nucleotide deletion located in exon 17 (of 58) of the NF1 gene alters the wild-type translational reading frame and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants in NF1 are known to be pathogenic. This variant was inherited from a parent who also has symptoms of NF1-related disorder. Based on the available evidence, the inherited c.1882del (p.Tyr628ThrfsTer3) variant in the NF1 gene is assessed as pathogenic. |
| ARUP Laboratories, |
RCV003738091 | SCV004564190 | pathogenic | not provided | 2023-10-31 | criteria provided, single submitter | clinical testing | The NF1 c.1882del; p.Tyr628ThrfsTer3 variant is reported in the literature in individuals affected with neurofibromatosis type 1 (Frayling 2019, Xu 2014). This variant is also reported in ClinVar (Variation ID: 1213688), but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with neurofibromatosis type 1 and are considered pathogenic (Frayling 2019, Wu-Chou 2018, Xu 2014). Based on available information, this variant is considered to be pathogenic. References: Frayling IM et al. Breast cancer risk in neurofibromatosis type 1 is a function of the type of NF1 gene mutation: a new genotype-phenotype correlation. J Med Genet. 2019 Apr;56(4):209-219. PMID: 30530636. Wu-Chou YH et al. Genetic diagnosis of neurofibromatosis type 1: targeted next- generation sequencing with Multiple Ligation-Dependent Probe Amplification analysis. J Biomed Sci. 2018 Oct 5;25(1):72. PMID: 30290804. Xu W et al. Fifty-four novel mutations in the NF1 gene and integrated analyses of the mutations that modulate splicing. Int J Mol Med. 2014 Jul;34(1):53-60. PMID: 24789688. |
| Department of Human Genetics, |
RCV004686682 | SCV005184176 | pathogenic | Neurofibromatosis, type 1 | 2024-08-07 | criteria provided, single submitter | clinical testing |