Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001043066 | SCV001206780 | uncertain significance | Neurofibromatosis, type 1 | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 342 of the NF1 protein (p.Ile342Val). 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: 840945). 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 with a negative 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 | RCV002379509 | SCV002689415 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-30 | criteria provided, single submitter | clinical testing | The p.I342V variant (also known as c.1024A>G), located in coding exon 9 of the NF1 gene, results from an A to G substitution at nucleotide position 1024. The isoleucine at codon 342 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Mayo Clinic Laboratories, |
RCV003480920 | SCV004224331 | uncertain significance | not provided | 2022-09-29 | criteria provided, single submitter | clinical testing | BP4, PM2 |
| St. |
RCV001043066 | SCV005402220 | uncertain significance | Neurofibromatosis, type 1 | 2024-03-07 | criteria provided, single submitter | clinical testing | The NF1 c.1024A>G (p.Ile342Val) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Neurofibromatosis type 1. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |