ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.4433C>A (p.Ala1478Glu) (rs143661911)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518326 SCV000615189 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing
Invitae RCV000550269 SCV000645259 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 1478 of the SETX protein (p.Ala1478Glu). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is present in population databases (rs143661911, ExAC 0.05%). This variant has been reported in an individual suspected to be affected with autosomal dominant amyotrophic lateral sclerosis, type 4.  This variant was also reported in an unaffected control subject. (PMID: 23129421). ClinVar contains an entry for this variant (Variation ID: 448329). 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. 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.
Fulgent Genetics,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 Clinical Services Laboratory,Illumina 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 Clinical Services Laboratory,Illumina 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.

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