ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.1009C>T (p.Arg337Ter) (rs386833517)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000404397 SCV000329726 pathogenic not provided 2017-03-31 criteria provided, single submitter clinical testing The R337X pathogenic variant in the GLDC gene has been reported previously in association with glycine encephalopathy in an affected individual who was compound heterozygous for the R337X variant and another variant (Conter et al., 2006). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R337X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret R337X as a pathogenic variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000049445 SCV000695755 pathogenic Non-ketotic hyperglycinemia 2016-10-14 criteria provided, single submitter clinical testing Variant summary: The GLDC c.1009C>T (p.Arg337X) variant results in a premature termination codon, predicted to cause a truncated or absent GLDC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/121360 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic GLDC variant (0.0026112). The variant has been reported in numerous affected individuals in the literature. In addition, one clinical diagnostic laboratory has classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000049445 SCV000946606 pathogenic Non-ketotic hyperglycinemia 2018-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg337*) in the GLDC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs386833517, ExAC 0.006%). This variant has been observed to be homozygous or in combination with another GLDC variant in several individuals affected with glycine encephalopathy (PMID: 26179960, 16601880). ClinVar contains an entry for this variant (Variation ID: 56036). Loss-of-function variants in GLDC are known to be pathogenic (PMID: 16601880). For these reasons, this variant has been classified as Pathogenic.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000404397 SCV001251720 pathogenic not provided 2020-05-03 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049445 SCV000081879 probable-pathogenic Non-ketotic hyperglycinemia no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Counsyl RCV000049445 SCV000790012 pathogenic Non-ketotic hyperglycinemia 2017-03-01 no assertion criteria provided clinical testing

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