ClinVar Miner

Submissions for variant NM_005787.6(ALG3):c.1061G>A (p.Arg354His)

gnomAD frequency: 0.00002  dbSNP: rs546890576
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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 RCV001361335 SCV001557308 pathogenic ALG3-congenital disorder of glycosylation 2022-11-29 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the Arg354 amino acid residue in ALG3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 34090370). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 ALG3 protein function. ClinVar contains an entry for this variant (Variation ID: 1053045). This missense change has been observed in individual(s) with congenital disorders of glycosylation and/or seizures (PMID: 27172925, 29667327). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs546890576, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 354 of the ALG3 protein (p.Arg354His).

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