Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002005645 | SCV002277206 | uncertain significance | Amyotrophic lateral sclerosis type 1 | 2021-10-15 | 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. This variant disrupts the p.His72 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been observed in individuals with SOD1-related conditions (PMID: 25681989), which suggests that this may be a clinically significant amino acid residue. 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 SOD1 protein function. This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with glutamine at codon 72 of the SOD1 protein (p.His72Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. |