Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002319142 | SCV001171543 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-01-30 | criteria provided, single submitter | clinical testing | The p.P458Q variant (also known as c.1373C>A), located in coding exon 12 of the NF1 gene, results from a C to A substitution at nucleotide position 1373. The proline at codon 458 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well 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. |
| Invitae | RCV002550763 | SCV002979456 | uncertain significance | Neurofibromatosis, type 1 | 2022-09-14 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 819038). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is present in population databases (rs781555047, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 458 of the NF1 protein (p.Pro458Gln). |