Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000611073 | SCV000730364 | likely benign | not specified | 2017-10-26 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Invitae | RCV000689563 | SCV000817219 | uncertain significance | Amyotrophic lateral sclerosis type 1 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 20 of the SOD1 protein (p.Asn20Ser). This variant is present in population databases (rs768029813, gnomAD 0.02%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis and in unaffected family members (PMID: 12783432, 14506936, 14755739, 21549454, 32951934). This variant is also known as N19S. ClinVar contains an entry for this variant (Variation ID: 516816). 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 SOD1 protein function. Experimental studies have shown that this missense change affects SOD1 function (PMID: 16035108). 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. |