Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002337074 | SCV001186648 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-03-20 | criteria provided, single submitter | clinical testing | The p.I1953V variant (also known as c.5857A>G), located in coding exon 39 of the NF1 gene, results from an A to G substitution at nucleotide position 5857. The isoleucine at codon 1953 is replaced by valine, 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. |
Invitae | RCV001862295 | SCV002109249 | uncertain significance | Neurofibromatosis, type 1 | 2021-02-21 | 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 not expected to disrupt NF1 protein function. This variant has not been reported in the literature in individuals with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 826011). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 1953 of the NF1 protein (p.Ile1953Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. |
Genome- |
RCV001862295 | SCV002560918 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |