ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.6733A>G (p.Met2245Val)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002369176 SCV002666942 uncertain significance Inborn genetic diseases 2019-09-06 criteria provided, single submitter clinical testing The p.M2245V variant (also known as c.6733A>G), located in coding exon 19 of the SETX gene, results from an A to G substitution at nucleotide position 6733. The methionine at codon 2245 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003098350 SCV003476410 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2022-04-28 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2245 of the SETX protein (p.Met2245Val). This variant is present in population databases (rs760039748, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SETX-related conditions. 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 not expected to disrupt SETX protein function. 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.
Genome-Nilou Lab RCV003234189 SCV003932060 uncertain significance Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003234190 SCV003932061 uncertain significance Amyotrophic lateral sclerosis type 4 2023-02-08 criteria provided, single submitter clinical testing

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