ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.3385G>A (p.Glu1129Lys)

gnomAD frequency: 0.00001  dbSNP: rs778505279
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220091 SCV001392064 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2019-05-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1129 of the SETX protein (p.Glu1129Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SETX-related conditions. This variant is present in population databases (rs778505279, ExAC 0.003%).
Ambry Genetics RCV002451502 SCV002618228 uncertain significance Inborn genetic diseases 2021-04-26 criteria provided, single submitter clinical testing The p.E1129K variant (also known as c.3385G>A), located in coding exon 8 of the SETX gene, results from a G to A substitution at nucleotide position 3385. The glutamic acid at codon 1129 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well 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.
Genome-Nilou Lab RCV003233999 SCV003931431 uncertain significance Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-02-08 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003234000 SCV003931432 uncertain significance Amyotrophic lateral sclerosis type 4 2023-02-08 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.