ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.799C>G (p.Pro267Ala)

gnomAD frequency: 0.00001  dbSNP: rs1554648117
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674678 SCV000800059 uncertain significance Glycine encephalopathy 2018-05-21 criteria provided, single submitter clinical testing
Mendelics RCV004698510 SCV001137746 likely pathogenic Glycine encephalopathy 1 2024-08-29 criteria provided, single submitter clinical testing Appeared in compund heterozygosis with a partial gene deletion (exons 1 tpo 15).
Labcorp Genetics (formerly Invitae), Labcorp RCV000674678 SCV001591331 pathogenic Glycine encephalopathy 2022-10-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 267 of the GLDC protein (p.Pro267Ala). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro267 amino acid residue in GLDC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26179960, 28244183; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects GLDC function (PMID: 28244183). 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. ClinVar contains an entry for this variant (Variation ID: 558413). This missense change has been observed in individual(s) with GLCD-related conditions (PMID: 27362913, 28244183). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency).

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