Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001048839 | SCV001212863 | uncertain significance | Neurofibromatosis, type 1 | 2022-05-26 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2323 of the NF1 protein (p.Thr2323Ile). This variant is not present in population databases (gnomAD no frequency). 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: 845721). 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. 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 | RCV002374894 | SCV002668299 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.T2323I variant (also known as c.6968C>T), located in coding exon 46 of the NF1 gene, results from a C to T substitution at nucleotide position 6968. The threonine at codon 2323 is replaced by isoleucine, 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. |