Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003499614 | SCV004281796 | uncertain significance | Exostoses, multiple, type 2 | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 254 of the EXT2 protein (p.Leu254Phe). This variant is present in population databases (rs768788739, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. 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 EXT2 protein function with a negative predictive value of 80%. 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 | RCV004369198 | SCV004866123 | uncertain significance | Inborn genetic diseases | 2023-10-03 | criteria provided, single submitter | clinical testing | The c.760C>T (p.L254F) alteration is located in exon 5 (coding exon 4) of the EXT2 gene. This alteration results from a C to T substitution at nucleotide position 760, causing the leucine (L) at amino acid position 254 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |