ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.871T>C (p.Cys291Arg)

dbSNP: rs141014950
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588380 SCV000695762 uncertain significance not provided 2016-12-06 criteria provided, single submitter clinical testing Variant summary: The GLDC c.871T>C (p.Cys291Arg) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this substitution (SNPs&GO not captured due to low reliability index). This variant is absent in 121004 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Labcorp Genetics (formerly Invitae), Labcorp RCV001860120 SCV002273199 likely pathogenic Glycine encephalopathy 2021-10-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 291 of the GLDC protein (p.Cys291Arg). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with glycine encephalopathy (PMID: 27362913). ClinVar contains an entry for this variant (Variation ID: 495701). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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