ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.3376T>G (p.Tyr1126Asp)

dbSNP: rs907569728
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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 RCV002043030 SCV002301443 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2021-07-17 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with aspartic acid at codon 1126 of the SETX protein (p.Tyr1126Asp). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. 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 not expected to disrupt SETX protein function. This variant has not been reported in the literature in individuals with SETX-related conditions. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV002458989 SCV002616843 uncertain significance Inborn genetic diseases 2021-02-02 criteria provided, single submitter clinical testing The p.Y1126D variant (also known as c.3376T>G), located in coding exon 8 of the SETX gene, results from a T to G substitution at nucleotide position 3376. The tyrosine at codon 1126 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and aspartic acid is the reference amino acid in other 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.
Genome-Nilou Lab RCV003234161 SCV003931434 uncertain significance Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003234162 SCV003931435 uncertain significance Amyotrophic lateral sclerosis type 4 2023-02-08 criteria provided, single submitter clinical testing

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