ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.5929C>T (p.Leu1977Phe)

gnomAD frequency: 0.00001  dbSNP: rs121434380
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV001288413 SCV001475494 likely pathogenic not provided 2019-12-19 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
GeneDx RCV001288413 SCV002571656 likely pathogenic not provided 2022-09-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24760770, 25725227, 25116135, 23129421, 19697368, 33333218, 24393486, 19696032, 17159128, 26147798)
Genome-Nilou Lab RCV000002385 SCV003931286 likely pathogenic Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-02-08 criteria provided, single submitter clinical testing
Invitae RCV003764517 SCV004569731 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2023-11-15 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1977 of the SETX protein (p.Leu1977Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of spinocerebellar ataxia (PMID: 17159128, 19696032). ClinVar contains an entry for this variant (Variation ID: 2295). 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 with a negative predictive value of 95%. Experimental studies have shown that this missense change affects SETX function (PMID: 25116135). 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.
OMIM RCV000002385 SCV000022543 pathogenic Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2006-12-12 no assertion criteria provided literature only

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.