Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002319190 | SCV001174421 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-04-30 | criteria provided, single submitter | clinical testing | The p.H647Q variant (also known as c.1941T>A), located in coding exon 17 of the NF1 gene, results from a T to A substitution at nucleotide position 1941. The histidine at codon 647 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003598021 | SCV004448692 | uncertain significance | Neurofibromatosis, type 1 | 2023-09-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 820388). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 647 of the NF1 protein (p.His647Gln). 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 not expected to disrupt 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. |