Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001928103 | SCV002184196 | uncertain significance | Neurofibromatosis, type 1 | 2021-10-18 | criteria provided, single submitter | clinical testing | A different nucleotide change at the same nucleotide position (c.1885G>A) resulting in the same protein effect (p.Gly629Arg) has been shown to affect splicing and has been reported as pathogenic (PMID: 12807981, 18546366, 23913538; Invitae). However, the effect of this variant (c.1885G>C) has not been experimentally evaluated and its effect on splicing is unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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 (ExAC no frequency). This sequence change replaces glycine with arginine at codon 629 of the NF1 protein (p.Gly629Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. |
| Division of Human Genetics, |
RCV001928103 | SCV003840175 | pathogenic | Neurofibromatosis, type 1 | no assertion criteria provided | research |