ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2614A>T (p.Lys872Ter) (rs1430968530)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526391 SCV000636391 pathogenic Non-ketotic hyperglycinemia 2018-01-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys872*) in the GLDC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported along with a second GLDC variant in individuals affected with non-ketotic hyperglycinaemia (PMID: 27362913). Loss-of-function variants in GLDC are known to be pathogenic (PMID: 16601880). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000526391 SCV000919468 likely pathogenic Non-ketotic hyperglycinemia 2018-05-25 criteria provided, single submitter clinical testing Variant summary: GLDC c.2614A>T (p.Lys872X) 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. A truncation downstream of this position has been classified as pathogenic by our laboratory (c.2891dupA (p.Tyr964X)). The variant was absent in 246210 control chromosomes (in gnomAD). c.2614A>T has been reported in the literature in individuals affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) (Coughlin 2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Counsyl RCV000526391 SCV000794973 pathogenic Non-ketotic hyperglycinemia 2017-10-24 no assertion criteria provided clinical testing

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