Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002304267 | SCV002589546 | uncertain significance | Neurofibromatosis, type 1 | 2022-07-21 | 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 affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 40 of the NF1 protein (p.Lys40Arg). |
Ambry Genetics | RCV002346580 | SCV002644951 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-08 | criteria provided, single submitter | clinical testing | The p.K40R variant (also known as c.119A>G), located in coding exon 2 of the NF1 gene, results from an A to G substitution at nucleotide position 119. The lysine at codon 40 is replaced by arginine, 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. |
Baylor Genetics | RCV004572128 | SCV005052263 | uncertain significance | Juvenile myelomonocytic leukemia | 2024-01-15 | criteria provided, single submitter | clinical testing |