ClinVar Miner

Submissions for variant NM_000454.5(SOD1):c.376G>C (p.Asp126His)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003064623 SCV003443856 uncertain significance Amyotrophic lateral sclerosis type 1 2022-07-11 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects SOD1 function (PMID: 16945901, 19483195, 19635794, 20399791, 23280792, 25600987, 26084641). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 variant is also known as p.Asp125His. This missense change has been observed in individual(s) with clinical features of amyotrophic lateral sclerosis (PMID: 8528216). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 126 of the SOD1 protein (p.Asp126His).

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