ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.1121G>A (p.Arg374Lys)

gnomAD frequency: 0.00006  dbSNP: rs141065026
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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 RCV001241746 SCV001414787 uncertain significance Glycine encephalopathy 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 374 of the GLDC protein (p.Arg374Lys). This variant is present in population databases (rs141065026, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GLDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 966949). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001751478 SCV001995680 uncertain significance not provided 2019-12-27 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; Missense variants in nearby residues reported in the Human Gene Mutation Database (Stenson et al., 2014)
Fulgent Genetics, Fulgent Genetics RCV001241746 SCV002791099 uncertain significance Glycine encephalopathy 2022-04-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002564008 SCV003696790 uncertain significance Inborn genetic diseases 2021-07-09 criteria provided, single submitter clinical testing The c.1121G>A (p.R374K) alteration is located in exon 8 (coding exon 8) of the GLDC gene. This alteration results from a G to A substitution at nucleotide position 1121, causing the arginine (R) at amino acid position 374 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001241746 SCV002075786 uncertain significance Glycine encephalopathy 2020-04-13 no assertion criteria provided clinical testing

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