Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002319274 | SCV001182383 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-08-05 | criteria provided, single submitter | clinical testing | The p.A1224G variant (also known as c.3671C>G), located in coding exon 27 of the NF1 gene, results from a C to G substitution at nucleotide position 3671. The alanine at codon 1224 is replaced by glycine, an amino acid with similar properties. This variant has been reported in a patient with a blastic plasmacytoid dendritic cell neoplasm (Szczepaniak A et al. Int. J. Hematol., 2019 Jul;110:102-106). 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 | RCV002549526 | SCV003484141 | uncertain significance | Neurofibromatosis, type 1 | 2022-05-20 | 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. 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: 824054). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 30977107). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1224 of the NF1 protein (p.Ala1224Gly). |