Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001045101 | SCV001208934 | pathogenic | Neurofibromatosis, type 1 | 2019-01-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). A different variant (c.1884C>A) giving rise to the same protein effect observed here (p.Tyr628*) has been determined to be pathogenic (Invitae). This suggests that this variant is also likely to be causative of disease. This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr628*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001045101 | SCV003845158 | likely pathogenic | Neurofibromatosis, type 1 | 2023-02-24 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.1884delC (p.Tyr628X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251210 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1884delC in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites this variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |