Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002319294 | SCV001183084 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-03-08 | criteria provided, single submitter | clinical testing | The p.S1311Y variant (also known as c.3932C>A), located in coding exon 29 of the NF1 gene, results from a C to A substitution at nucleotide position 3932. The serine at codon 1311 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well 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 | RCV003598032 | SCV004540088 | uncertain significance | Neurofibromatosis, type 1 | 2022-11-08 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 824397). 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 serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1311 of the NF1 protein (p.Ser1311Tyr). |