Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002020327 | SCV002289371 | likely pathogenic | Amyotrophic lateral sclerosis type 1 | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 23 of the SOD1 protein (p.Gln23His). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with autosomal dominant amyotrophic lateral sclerosis (PMID: 21603025). This variant is also known as Q22H. ClinVar contains an entry for this variant (Variation ID: 1505077). 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 with a positive predictive value of 95%. This variant disrupts the p.Gln23 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23280792, 32951934). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Prevention |
RCV003408072 | SCV004112815 | likely pathogenic | SOD1-related disorder | 2023-05-16 | criteria provided, single submitter | clinical testing | The SOD1 c.69G>C variant is predicted to result in the amino acid substitution p.Gln23His. This variant was reported in a patient with sporadic amyotrophic lateral sclerosis (described as p.Q22H, Akimoto et al. 2011. PubMed ID: 21603025). Other substitutions (Leu, Arg) at this amino acid position have been reported as pathogenic (described as Q22L, Ungaro et al. 2020. PubMed ID: 32951934; Corti et al. 2009. PubMed ID: 19000626). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-33032151-G-C). This variant is interpreted as likely pathogenic. |
| Mayo Clinic Laboratories, |
RCV004793695 | SCV005410127 | uncertain significance | not provided | 2024-04-10 | criteria provided, single submitter | clinical testing | PP3, PM2, PM5 |