Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000993040 | SCV001145741 | likely pathogenic | not provided | 2019-01-14 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality (0/250484 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Damaging to protein function(s) relevant to disease mechanism. |
| Invitae | RCV001858765 | SCV002238431 | pathogenic | Amyotrophic lateral sclerosis type 1 | 2021-12-02 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 805494). This variant is also known as p.D76Y. This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 9365366, 18428003, 23286750, 25382069, 28430856). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 77 of the SOD1 protein (p.Asp77Tyr). Experimental studies have shown that this missense change affects SOD1 function (PMID: 19635794, 20189984, 23280792). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp77 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12215228; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. |