Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002380464 | SCV002673592 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-03-23 | criteria provided, single submitter | clinical testing | The p.Y2464S variant (also known as c.7391A>C), located in coding exon 49 of the NF1 gene, results from an A to C substitution at nucleotide position 7391. The tyrosine at codon 2464 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not 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. |
| Labcorp Genetics |
RCV003598109 | SCV004451593 | uncertain significance | Neurofibromatosis, type 1 | 2023-04-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1758668). 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. 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. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 2464 of the NF1 protein (p.Tyr2464Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). |