Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002389981 | SCV002699434 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2016-06-27 | criteria provided, single submitter | clinical testing | The p.A502P variant (also known as c.1504G>C), located in coding exon 13 of the NF1 gene, results from a G to C substitution at nucleotide position 1504. The alanine at codon 502 is replaced by proline, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6500 samples (13000 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV005097555 | SCV005732522 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 502 of the NF1 protein (p.Ala502Pro). 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: 1774064). 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. 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. |