Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004994578 | SCV005451985 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-08-05 | criteria provided, single submitter | clinical testing | The p.P2654R variant (also known as c.7961C>G), located in coding exon 54 of the NF1 gene, results from a C to G substitution at nucleotide position 7961. The proline at codon 2654 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV005000590 | SCV005624667 | uncertain significance | not provided | 2024-05-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005107601 | SCV005732420 | uncertain significance | Neurofibromatosis, type 1 | 2024-05-16 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2654 of the NF1 protein (p.Pro2654Arg). 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. 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 not expected to disrupt NF1 protein function with a negative predictive value of 95%. 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. |