Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002391080 | SCV001188079 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-02-07 | criteria provided, single submitter | clinical testing | The p.G2313S variant (also known as c.6937G>A), located in coding exon 46 of the NF1 gene, results from a G to A substitution at nucleotide position 6937. The glycine at codon 2313 is replaced by serine, an amino acid with similar properties. 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. |
| Invitae | RCV002551938 | SCV003196596 | likely pathogenic | Neurofibromatosis, type 1 | 2022-05-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2313 of the NF1 protein (p.Gly2313Ser). 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. This variant disrupts the p.Gly2313 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21520333, 26740943; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 826712). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). |