Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001217858 | SCV001389716 | uncertain significance | Hereditary motor and sensory neuropathy, Okinawa type; Hereditary spastic paraplegia 57 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 326 of the TFG protein (p.Ala326Ser). This variant is present in population databases (rs776620173, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TFG-related conditions. ClinVar contains an entry for this variant (Variation ID: 946901). 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 TFG 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. |
| Gene |
RCV002473224 | SCV002769857 | uncertain significance | not provided | 2022-06-21 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |