ClinVar Miner

Submissions for variant NM_000178.4(GSS):c.709C>T (p.Arg237Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001042779 SCV001206481 pathogenic Gluthathione synthetase deficiency 2019-02-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg237*) in the GSS gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs201925123, ExAC 0.003%). This variant has been observed in combination with another GSS variant in an individual affected with gluthathione synthetase deficiency (PMID: 15717202). Loss-of-function variants in GSS are known to be pathogenic (PMID: 12638941, 15717202). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001042779 SCV001337770 likely pathogenic Gluthathione synthetase deficiency 2020-01-13 criteria provided, single submitter clinical testing Variant summary: GSS c.709C>T (p.Arg237X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.8e-05 in 251492 control chromosomes (gnomAD). c.709C>T has been reported in the literature in one compound heterozygous individual affected with Glutathione Synthetase Deficiency (Njalsson_2005). These data do not allow any conclusion about variant significance. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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