ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.2311G>A (p.Gly771Arg)

gnomAD frequency: 0.00004  dbSNP: rs386833553
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000049481 SCV000636381 pathogenic Glycine encephalopathy 2024-06-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 771 of the GLDC protein (p.Gly771Arg). This variant is present in population databases (rs386833553, gnomAD 0.005%). This missense change has been observed in individual(s) with nonketotic hyperglycinemia (PMID: 16450403, 17361008, 27362913). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 56072). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GLDC protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000049481 SCV000791590 likely pathogenic Glycine encephalopathy 2017-05-17 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000049481 SCV002024842 pathogenic Glycine encephalopathy 2021-05-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000049481 SCV003844996 pathogenic Glycine encephalopathy 2023-02-20 criteria provided, single submitter clinical testing Variant summary: GLDC c.2311G>A (p.Gly771Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249518 control chromosomes. c.2311G>A has been reported in the literature in multiple individuals affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) including homozygous, compound heterozygous (confirmed in trans) and even a de novo patient (Kure_2006, Kanno_2007, Coughlin_2017). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049481 SCV000081915 probable-pathogenic Glycine encephalopathy no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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