Total submissions: 5
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. |
Gene |
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- |
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 |