ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.1009C>T (p.Arg337Ter)

gnomAD frequency: 0.00003  dbSNP: rs386833517
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000404397 SCV000329726 pathogenic not provided 2022-06-07 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16601880, 28714951, 27362913, 26179960, 31980526)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000049445 SCV000695755 pathogenic Glycine encephalopathy 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000049445 SCV000946606 pathogenic Glycine encephalopathy 2024-01-04 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. Loss-of-function variants in GLDC are known to be pathogenic (PMID: 16601880). This variant is present in population databases (rs386833517, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with glycine encephalopathy (PMID: 16601880, 26179960). ClinVar contains an entry for this variant (Variation ID: 56036). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV004566898 SCV005051798 pathogenic Glycine encephalopathy 1 2024-02-01 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV004566898 SCV005679333 pathogenic Glycine encephalopathy 1 2024-03-21 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049445 SCV000081879 probable-pathogenic Glycine encephalopathy no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Counsyl RCV000049445 SCV000790012 pathogenic Glycine encephalopathy 2017-03-01 no assertion criteria provided clinical testing
Natera, Inc. RCV000049445 SCV002075789 pathogenic Glycine encephalopathy 2021-03-18 no assertion criteria provided clinical testing

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