Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002017999 | SCV002303534 | uncertain significance | Neurofibromatosis, type 1 | 2022-11-25 | 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 467 of the NF1 protein (p.Thr467Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 19076627). This variant is also known as c.1611C>T. ClinVar contains an entry for this variant (Variation ID: 1509567). 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 | RCV002389028 | SCV002702370 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-11-27 | criteria provided, single submitter | clinical testing | The p.T467I variant (also known as c.1400C>T), located in coding exon 13 of the NF1 gene, results from a C to T substitution at nucleotide position 1400. The threonine at codon 467 is replaced by isoleucine, an amino acid with similar properties. This variant has been identified in an individual with clinical NF1 whose disease has been attributed to a co-occurring NF1 truncating variant (Bongiorno MR et al. Dermatol Ther;21 Suppl 3:S21-5). 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. |