ClinVar Miner

Submissions for variant NM_025215.6(PUS1):c.717C>A (p.Tyr239Ter) (rs779651314)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000454345 SCV000538058 likely pathogenic Myopathy, lactic acidosis, and sideroblastic anemia 1 2015-09-26 criteria provided, single submitter clinical testing The c.633C>A (p.Tyr211ter) novel nonsense variant in the PUS1 gene is predicted to cause a premature protein truncation that lacks 188 amino acids (NP_001002020) in the C-terminal region of the protein. The C-terminal portion, which is predicted to be deleted as a result of this variant, comprises three helices that are necessary to maintain structural integrity and stability (Czudnochowski N et al., 2013). Indeed, a mutant form of hPus1 that lacks the important three helical domains in the C-terminal end was unable to solubilize (Czudnochowski N et al., 2013). Furthermore, Fernandez-Vizarra E et al. (2007) reported that two brothers who were affected with MLASA carried a homozygous variant (p.Glu192ter) that was also predicted to ablate the three C-terminal helices of the protein. This locus is conserved across species. The frequency of this variant is either absent or very low in the population databases (1000 Genome, Exome Sequencing Project and ExAC)

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