Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000437840 | SCV000528304 | uncertain significance | not provided | 2016-05-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ALG13 gene. The S25N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 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 S25N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Fulgent Genetics, |
RCV002506054 | SCV002815997 | uncertain significance | Developmental and epileptic encephalopathy, 36 | 2021-08-25 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002506054 | SCV003292555 | uncertain significance | Developmental and epileptic encephalopathy, 36 | 2023-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 25 of the ALG13 protein (p.Ser25Asn). 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: 386579). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |