Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000464751 | SCV000542100 | uncertain significance | Neurofibromatosis, type 1 | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 2326 of the NF1 protein (p.Ser2326Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 404518). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002374745 | SCV002667994 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-04 | criteria provided, single submitter | clinical testing | The p.S2326G variant (also known as c.6976A>G), located in coding exon 46 of the NF1 gene, results from an A to G substitution at nucleotide position 6976. The serine at codon 2326 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002481366 | SCV002776163 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-12-22 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004551510 | SCV004800528 | uncertain significance | NF1-related disorder | 2024-02-21 | criteria provided, single submitter | clinical testing | The NF1 c.7039A>G variant is predicted to result in the amino acid substitution p.Ser2347Gly. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |