Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001373417 | SCV001570132 | uncertain significance | Neurofibromatosis, type 1 | 2023-08-28 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2370 of the NF1 protein (p.Val2370Ala). 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: 1063567). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. This variant disrupts the p.Val2370 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23954459; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |
| Ambry Genetics | RCV002368208 | SCV002664159 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-07-12 | criteria provided, single submitter | clinical testing | The p.V2370A variant (also known as c.7109T>C), located in coding exon 47 of the NF1 gene, results from a T to C substitution at nucleotide position 7109. The valine at codon 2370 is replaced by alanine, an amino acid with similar properties. 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. |
| Breakthrough Genomics, |
RCV004692672 | SCV005192807 | uncertain significance | not provided | criteria provided, single submitter | not provided |