Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000518527 | SCV000615367 | pathogenic | not provided | 2017-03-09 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000015887 | SCV000962776 | pathogenic | Amyotrophic lateral sclerosis type 1 | 2024-05-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 5 of the SOD1 protein (p.Ala5Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal dominant amyotrophic lateral sclerosis (PMID: 8179602, 12792143, 17543992, 22292843). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Ala4Thr. ClinVar contains an entry for this variant (Variation ID: 14765). 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%. Experimental studies have shown that this missense change affects SOD1 function (PMID: 8179602, 17543992, 21257910, 23280792, 26362407). This variant disrupts the p.Ala5 amino acid residue in SOD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7951249, 8351519, 19176896, 19618436). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, |
RCV000015887 | SCV001251043 | pathogenic | Amyotrophic lateral sclerosis type 1 | 2020-03-31 | criteria provided, single submitter | research | |
| OMIM | RCV000015887 | SCV000036154 | pathogenic | Amyotrophic lateral sclerosis type 1 | 1994-06-11 | no assertion criteria provided | literature only |