Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001059628 | SCV001224255 | uncertain significance | Neurofibromatosis, type 1 | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 227 of the NF1 protein (p.Tyr227His). This variant is present in population databases (rs780682850, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 854550). 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 with a positive 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. |
| Ambry Genetics | RCV002365730 | SCV002666292 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-15 | criteria provided, single submitter | clinical testing | The p.Y227H variant (also known as c.679T>C), located in coding exon 7 of the NF1 gene, results from a T to C substitution at nucleotide position 679. The tyrosine at codon 227 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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. |