Submissions for variant NM_001099922.3(ALG13):c.632A>G (p.Tyr211Cys)

dbSNP: rs1556483387

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498462	SCV000589699	likely pathogenic	not provided	2015-11-25	criteria provided, single submitter	clinical testing	The Y211C variant in the ALG13 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y211C variant was not observed in approximately 5,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Y211C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The Y211C variant is a strong candidate for a pathogenic variant
Invitae	RCV003651941	SCV004388911	uncertain significance	Developmental and epileptic encephalopathy, 36	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 211 of the ALG13 protein (p.Tyr211Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALG13-related conditions. ClinVar contains an entry for this variant (Variation ID: 432029). 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 not expected to disrupt ALG13 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.