Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002394088 | SCV002669863 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2017-09-28 | criteria provided, single submitter | clinical testing | The p.H2525P variant (also known as c.7574A>C), located in coding exon 51 of the NF1 gene, results from an A to C substitution at nucleotide position 7574. The histidine at codon 2525 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003103417 | SCV003346235 | uncertain significance | Neurofibromatosis, type 1 | 2022-04-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NF1-related conditions. 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. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 2525 of the NF1 protein (p.His2525Pro). |
| Gene |
RCV003324854 | SCV004030747 | uncertain significance | not provided | 2023-02-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |