Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002032937 | SCV002112405 | uncertain significance | Neurofibromatosis, type 1 | 2021-03-29 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with leucine at codon 932 of the NF1 protein (p.Met932Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. This variant has been observed in individual(s) with breast cancer (PMID: 33471991). 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. |
| Ambry Genetics | RCV002440905 | SCV002748318 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-08-30 | criteria provided, single submitter | clinical testing | The p.M932L variant (also known as c.2794A>C), located in coding exon 21 of the NF1 gene, results from an A to C substitution at nucleotide position 2794. The methionine at codon 932 is replaced by leucine, 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. |