Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000818105 | SCV000958702 | likely pathogenic | Neurofibromatosis, type 1 | 2024-03-04 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2104 of the NF1 protein (p.Leu2104Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 24413922). ClinVar contains an entry for this variant (Variation ID: 660822). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV001585754 | SCV001813943 | uncertain significance | not provided | 2019-06-03 | criteria provided, single submitter | clinical testing | Identified in a father and son who were clinically diagnosed with NF1 according to NIH 1987 guidelines (Ben-Salem et al., 2014) Not observed in large population cohorts (Lek et al., 2016) In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect De novo variant with confirmed parentage, but the reported clinical features of this patient are not consistent with the clinical criteria necessary to make a diagnosis of an NF1-related disorder This variant is associated with the following publications: (PMID: 24413922) |
| Genome- |
RCV000818105 | SCV002560960 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Al Jalila Children’s Genomics Center, |
RCV004798876 | SCV005420508 | likely pathogenic | Café-au-lait macules with pulmonary stenosis | 2024-10-04 | criteria provided, single submitter | research | PM2,PP3,PP1,PM5 |