Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000015892 | SCV002289500 | likely pathogenic | Amyotrophic lateral sclerosis type 1 | 2022-09-07 | criteria provided, single submitter | clinical testing | 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. Experimental studies have shown that this missense change affects SOD1 function (PMID: 23280792). 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: 14769). This variant is also known as p.Ala145Thr. This missense change has been observed in individuals with amyotrophic lateral sclerosis (ALS) (PMID: 7496169, 14506936, 22292843). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 146 of the SOD1 protein (p.Ala146Thr). |
OMIM | RCV000015892 | SCV000036159 | pathogenic | Amyotrophic lateral sclerosis type 1 | 1995-09-01 | no assertion criteria provided | literature only |