ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.668T>A (p.Leu223His)

dbSNP: rs1211053963
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000992952 SCV001145569 uncertain significance not provided 2019-01-16 criteria provided, single submitter clinical testing
GeneDx RCV000992952 SCV001992369 uncertain significance not provided 2019-10-03 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV003233904 SCV003931574 uncertain significance Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003233905 SCV003931575 uncertain significance Amyotrophic lateral sclerosis type 4 2023-02-08 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003411936 SCV004107718 uncertain significance SETX-related condition 2023-05-25 criteria provided, single submitter clinical testing The SETX c.668T>A variant is predicted to result in the amino acid substitution p.Leu223His. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Invitae RCV003769316 SCV004592605 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-03-16 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 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. ClinVar contains an entry for this variant (Variation ID: 805429). This variant has not been reported in the literature in individuals affected with SETX-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 223 of the SETX protein (p.Leu223His).

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