Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002330331 | SCV002634186 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-12-06 | criteria provided, single submitter | clinical testing | The p.F1515S variant (also known as c.4544T>C), located in coding exon 34 of the NF1 gene, results from a T to C substitution at nucleotide position 4544. The phenylalanine at codon 1515 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003598082 | SCV004547719 | pathogenic | Neurofibromatosis, type 1 | 2023-06-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 1741383). This missense change has been observed in individual(s) with NF1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1515 of the NF1 protein (p.Phe1515Ser). |