Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001918459 | SCV002180445 | uncertain significance | Legius syndrome | 2024-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 102 of the SPRED1 protein (p.Thr102Met). This variant is present in population databases (rs754706111, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of Legius syndrome (PMID: 26635368). ClinVar contains an entry for this variant (Variation ID: 1407466). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SPRED1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SPRED1 function (PMID: 26635368). This variant disrupts the p.Thr102 amino acid residue in SPRED1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19920235, 21089071, 22751498, 31401120; internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| NHS Central & South Genomic Laboratory Hub | RCV004782822 | SCV005393959 | likely pathogenic | Neurofibromatosis, type 1 | 2024-11-11 | criteria provided, single submitter | clinical testing |