ClinVar Miner

Submissions for variant NM_000454.5(SOD1):c.449T>C (p.Ile150Thr)

gnomAD frequency: 0.00001  dbSNP: rs1424014997
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001942245 SCV002228234 pathogenic Amyotrophic lateral sclerosis type 1 2021-11-25 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. This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 150 of the SOD1 protein (p.Ile150Thr). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individuals with autosomal dominant amyotrophic lateral sclerosis (PMID: 7887412, 28709720). It has also been observed to segregate with disease in related individuals. Experimental studies have shown that this missense change affects SOD1 function (PMID: 20404329, 23280792, 23872456). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics RCV002473336 SCV002771831 pathogenic not provided 2022-01-06 criteria provided, single submitter clinical testing This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls; therefore, The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant appears to segregate with disease in at least one family. This variant is also referred to as p.Ile149Thr in published literature. Computational tools predict that this variant is damaging.
Mayo Clinic Laboratories, Mayo Clinic RCV002473336 SCV004225360 likely pathogenic not provided 2022-02-08 criteria provided, single submitter clinical testing PP1, PP3, PM1, PM2, PS4_moderate
PreventionGenetics, part of Exact Sciences RCV004746543 SCV005362561 pathogenic SOD1-related disorder 2024-08-09 no assertion criteria provided clinical testing The SOD1 c.449T>C variant is predicted to result in the amino acid substitution p.Ile150Thr. This variant, previously described as p.Ile149Thr using legacy nomenclature, has been reported to be causative for amyotrophic lateral sclerosis (Pang et al. 2017. PubMed ID: 28709720; Pramatarova et al. 1995. PubMed ID: 7887412; Brown et al. 2012. PubMed ID: 22292843). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-33040875-T-C) and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1455194/). This variant is interpreted as pathogenic.

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