ClinVar Miner

Submissions for variant NM_007375.3(TARDBP):c.269C>T (p.Ala90Val) (rs80356715)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000821536 SCV000962295 uncertain significance Amyotrophic lateral sclerosis type 10; TARDBP-related frontotemporal dementia 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 90 of the TARDBP protein (p.Ala90Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs80356715, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in several individuals affected with amyotrophic lateral sclerosis and has also been reported in unaffected individuals (PMID: 18505686, 28430856, 18309045, 18545701, 22645277, 18372902, 20555136, 23327806, 19224587, 19760257, 28889094). ClinVar contains an entry for this variant (Variation ID: 21481). While some experimental studies have shown that this missense change produces a modest deleterious effect on the TARDBP protein, other studies have shown that this effect is not strong enough to produce disease (PMID: 18505686, 24143176, 26883171, 25442115, 28335005, 28286471). 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.
Illumina Clinical Services Laboratory,Illumina RCV000020670 SCV001258292 uncertain significance Amyotrophic lateral sclerosis type 10 2017-04-27 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.
GeneReviews RCV000020670 SCV000041208 uncertain significance Amyotrophic lateral sclerosis type 10 2015-03-12 no assertion criteria provided literature only May be a variant that is normal or confers susceptibility to FTD/ALS.

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