ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.1951C>G (p.His651Asp)

dbSNP: rs2129735272
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001902855 SCV002152932 likely pathogenic Glycine encephalopathy 2024-02-27 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 651 of the GLDC protein (p.His651Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features consistent with glycine encephalopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 1385319). 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%. This variant disrupts the p.His651 amino acid residue in GLDC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16601880, 27362913). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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