Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000687912 | SCV000815504 | pathogenic | Amyotrophic lateral sclerosis type 1 | 2023-08-10 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects SOD1 function (PMID: 23280792). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 90 of the SOD1 protein (p.Ala90Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant SOD1-related conditions (PMID: 34518333; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as A89T. ClinVar contains an entry for this variant (Variation ID: 567744). 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. For these reasons, this variant has been classified as Pathogenic. |
| Athena Diagnostics | RCV000713398 | SCV000843999 | uncertain significance | not provided | 2017-12-20 | criteria provided, single submitter | clinical testing | |
| Servicio Canario de Salud, |
RCV000687912 | SCV004041594 | uncertain significance | Amyotrophic lateral sclerosis type 1 | 2023-10-06 | criteria provided, single submitter | clinical testing | The c.268G>A, p.(Ala90Thr) SOD1 variant in heterocigous state has been reported in our laboratory in a 75-year-old female patient with a clinical diagnosis of motor neuron myopathy. Two brothers and an aunt with same diagnostic (not tested, deceased). This variant has been reported in an individual with Amyotrophic Lateral Sclerosis (PMID: 14506936). This variant was absent from large population studies (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 567744). In silico analysis (CADD, Revel) are inconclusive, but this prediction has not been confirmed by functional studies. In summary, the available evidence for c.268G>A, p.(Ala90Thr) SOD1 variant is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |