Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001036624 | SCV001199997 | pathogenic | Neurofibromatosis, type 1 | 2023-01-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys1909Tyrfs*5) in the NF1 gene. It is expected to result in an absent or disrupted protein product. 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). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 25074460). ClinVar contains an entry for this variant (Variation ID: 835683). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001576311 | SCV001803470 | pathogenic | not provided | 2021-01-13 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 25074460) |
| Genome- |
RCV001036624 | SCV002560146 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001036624 | SCV005886237 | pathogenic | Neurofibromatosis, type 1 | 2025-02-07 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.5726_5727delGT (p.Cys1909TyrfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251096 control chromosomes. c.5726_5727delGT has been reported in the literature in at least one individual affected with Neurofibromatosis Type 1 (e.g. Pasmant_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 25074460). ClinVar contains an entry for this variant (Variation ID: 835683). Based on the evidence outlined above, the variant was classified as pathogenic. |