ClinVar Miner

Submissions for variant NM_000113.2(TOR1A):c.907_909delGAG (p.Glu303del) (rs80358233)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000584141 SCV000692306 pathogenic Dystonia 2017-01-26 no assertion criteria provided clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000412981 SCV000854896 pathogenic not provided 2018-03-21 criteria provided, single submitter clinical testing
GeneDx RCV000412981 SCV000491317 pathogenic not provided 2018-12-03 criteria provided, single submitter clinical testing The c.907_909delGAG pathogenic variant is the most common pathogenic variant associated with DYT1-related primary dystonia and has been reported as both an inherited variant in familial cases and a de novo variant in several individuals (Ozelius et al., 1997; Hjermind et al., 2002; Saunders-Pullman et al., 2014). The c.907_909delGAG variant has also been reported in the homozygous state or in trans with another TOR1A variant in several individuals with arthrogryposis (Reichert et al., 2017; Kariminejad et al., 2017). This variant is an in-frame deletion that results in the loss of a single Glutamic Acid residue, denoted p.Glu303del. Functional studies demonstrate that the c.907_909delGAG variant results in abnormal cellular localization and aggregation of the misfolded protein (Gordon et al., 2008; Hettich et al., 2014). The c.907_909delGAG variant is observed in 16/10,152 (0.16%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). We interpret c.907_909delGAG as a pathogenic variant.
GeneReviews RCV000005488 SCV000040443 pathogenic Dystonia 1 2016-11-17 no assertion criteria provided literature only
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000005488 SCV000778594 likely pathogenic Dystonia 1 2018-05-10 criteria provided, single submitter research
Invitae RCV000584141 SCV000283510 pathogenic Dystonia 2019-01-07 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 5 of the TOR1A mRNA (c.907_909delGAG). This leads to the deletion of 1 amino acid residue in the TOR1A protein (p.Glu303del) but otherwise preserves the integrity of the reading frame. This variant is clearly defined as a causative allele for early onset primary dystonia (PMID: 9288096, 9874484, 11973627, 12481989, 24930953, 24931141). It is estimated to have a penetrance of between 30 to 40% (PMID: 20301665). ClinVar contains an entry for this variant (Variation ID: 5180). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005488 SCV000025670 pathogenic Dystonia 1 2014-09-01 no assertion criteria provided literature only

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