ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.1691G>T (p.Ser564Ile)

gnomAD frequency: 0.00016  dbSNP: rs121964974
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000012762 SCV002154353 pathogenic Glycine encephalopathy 2023-10-10 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 564 of the GLDC protein (p.Ser564Ile). This variant is present in population databases (rs121964974, gnomAD 0.2%). This missense change has been observed in individual(s) with glycine encephalopathy and/or nonketotic hyperglycinemia (PMID: 1634607, 27362913). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 11982). 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. Experimental studies have shown that this missense change affects GLDC function (PMID: 1634607, 15192636, 15236413, 15824356). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000012762 SCV003828287 likely pathogenic Glycine encephalopathy 2021-11-23 criteria provided, single submitter clinical testing
OMIM RCV004566730 SCV000032997 pathogenic Glycine encephalopathy 1 1992-07-01 no assertion criteria provided literature only
GeneReviews RCV000012762 SCV000086735 pathologic Glycine encephalopathy 2013-07-11 no assertion criteria provided curation Converted during submission to Pathogenic.

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