Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001378152 | SCV001575653 | likely pathogenic | Neurofibromatosis, type 1 | 2020-10-19 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Phe1193 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with isoleucine at codon 1193 of the NF1 protein (p.Phe1193Ile). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and isoleucine. |
| Ambry Genetics | RCV004557577 | SCV005047740 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-11-09 | criteria provided, single submitter | clinical testing | The p.F1193I variant (also known as c.3577T>A), located in coding exon 27 of the NF1 gene, results from a T to A substitution at nucleotide position 3577. The phenylalanine at codon 1193 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |