Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000632428 | SCV000753608 | uncertain significance | Neurofibromatosis, type 1 | 2017-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with proline at codon 2532 of the NF1 protein (p.Ala2532Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV003162811 | SCV003861688 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-01-31 | criteria provided, single submitter | clinical testing | The p.A2532P variant (also known as c.7594G>C), located in coding exon 51 of the NF1 gene, results from a G to C substitution at nucleotide position 7594. The alanine at codon 2532 is replaced by proline, an amino acid with highly 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. |