Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000706500 | SCV000835554 | likely pathogenic | Neurofibromatosis, type 1 | 2024-02-26 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1620 of the NF1 protein (p.Ile1620Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 30014477). ClinVar contains an entry for this variant (Variation ID: 582432). 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 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. |
| Ambry Genetics | RCV002334390 | SCV002639465 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-03-11 | criteria provided, single submitter | clinical testing | The p.I1620T variant (also known as c.4859T>C), located in coding exon 36 of the NF1 gene, results from a T to C substitution at nucleotide position 4859. The isoleucine at codon 1620 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in an Italian patient referred for neurofibromatosis type I (NF1) testing (Bianchessi D et al. Mol Genet Genomic Med, 2015 Nov;3:513-25) and in a Spanish patient who met NF1 diagnostic criteria (Palma Milla C et al. Ann Hum Genet, 2018 11;82:425-436). This amino acid position is highly conserved in available vertebrate species. 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. |
| Gene |
RCV004777852 | SCV005391897 | uncertain significance | not provided | 2024-04-30 | criteria provided, single submitter | clinical testing | Observed in individuals reported to have features consistent with NF1-related neurofibromatosis (PMID: 26740943, 30014477); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: Morosini2014[thesis], 26740943, 30014477) |