Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001062926 | SCV001227752 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 1C | 2022-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 382 of the SPTLC2 protein (p.Gly382Arg). This variant is not present in population databases (gnomAD no frequency). 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. This variant disrupts the p.Gly382 amino acid residue in SPTLC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20920666, 24175284, 26681808). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt SPTLC2 protein function. ClinVar contains an entry for this variant (Variation ID: 857284). This missense change has been observed in individual(s) with inherited peripheral neuropathy (PMID: 27549087). |