Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002040384 | SCV002300422 | uncertain significance | Neurofibromatosis, type 1 | 2021-02-07 | 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. This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with tyrosine at codon 564 of the NF1 protein (p.Asp564Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. |
| Ambry Genetics | RCV004558800 | SCV005048538 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-12-04 | criteria provided, single submitter | clinical testing | The p.D564Y variant (also known as c.1690G>T), located in coding exon 15 of the NF1 gene, results from a G to T substitution at nucleotide position 1690. The aspartic acid at codon 564 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |