Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001884749 | SCV002158176 | uncertain significance | Neurofibromatosis, type 1 | 2021-11-19 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 489 of the NF1 protein (p.Tyr489His). |
| Ambry Genetics | RCV002388785 | SCV002696316 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-09-30 | criteria provided, single submitter | clinical testing | The p.Y489H variant (also known as c.1465T>C), located in coding exon 13 of the NF1 gene, results from a T to C substitution at nucleotide position 1465. The tyrosine at codon 489 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |