Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV001644615 | SCV000615189 | benign | not specified | 2020-11-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000550269 | SCV000645259 | likely benign | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2023-12-06 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000550269 | SCV000895959 | uncertain significance | Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001165737 | SCV001327968 | uncertain significance | Amyotrophic lateral sclerosis type 4 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001167321 | SCV001329801 | uncertain significance | Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Mayo Clinic Laboratories, |
RCV000518326 | SCV001716041 | uncertain significance | not provided | 2019-11-03 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000518326 | SCV001817190 | uncertain significance | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | Observed in an individual with corticobasal syndrome who had a loss of function variant in another gene associated with this disorder, and the authors concluded that the SETX variant was unlikely to be the cause the disorder (Seibert et al., 2022); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28642336, 23129421, 32409511, 35309588) |
Genome Diagnostics Laboratory, |
RCV001848902 | SCV002105158 | uncertain significance | Hereditary spastic paraplegia | 2019-07-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002329225 | SCV002628306 | uncertain significance | Inborn genetic diseases | 2022-03-11 | criteria provided, single submitter | clinical testing | The p.A1478E variant (also known as c.4433C>A), located in coding exon 8 of the SETX gene, results from a C to A substitution at nucleotide position 4433. The alanine at codon 1478 is replaced by glutamic acid, an amino acid with dissimilar properties. This alteration was reported in a female with symmetrical lower limb amyotrophic paraparesis, onset in middle age. The alteration was absent in two healthy family members and was present in sample from her deceased father, who had generalized muscular atrophy; it was also present in one unrelated unaffected German control included in the study (Arning L et al. Neurogenetics, 2013 Feb;14:53-61). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant juvenile amyotrophic lateral sclerosis 4; however, its contribution to the development of autosomal recessive spinocerebellar ataxia with axonal neuropathy 2 is uncertain. |
Prevention |
RCV003431059 | SCV004116619 | uncertain significance | SETX-related condition | 2024-01-08 | criteria provided, single submitter | clinical testing | The SETX c.4433C>A variant is predicted to result in the amino acid substitution p.Ala1478Glu. This variant was reported in individuals with amyotrophic lateral sclerosis (Arning et al. 2013. PubMed ID: 23129421; McCann et al. 2020. PubMed ID: 32409511) as well as in unaffected controls (Arning et al. 2013. PubMed ID: 23129421). This variant is reported in 0.052% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too common to be a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Ce |
RCV000518326 | SCV004156608 | uncertain significance | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing |