Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000497787 | SCV000589306 | uncertain significance | not provided | 2017-05-31 | criteria provided, single submitter | clinical testing | The D1091H variant in the ALG13 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D1091H variant is not observed in large population cohorts, however, this variant has been detected in the hemizygous state in at least one presumably healthy individual tested at GeneDx (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D1091H 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. However, this substitution occurs at a position that is not conserved and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on review of the data in the context of the 2015 ACMG standards and guidelines for the interpretation of sequence variants (Richards et al., 2015), we now interpret D1091H as a variant of uncertain significance. |
Labcorp Genetics |
RCV001865558 | SCV002214133 | uncertain significance | Developmental and epileptic encephalopathy, 36 | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1091 of the ALG13 protein (p.Asp1091His). 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: 431802). 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 disruptive. 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. |
Fulgent Genetics, |
RCV001865558 | SCV002807022 | uncertain significance | Developmental and epileptic encephalopathy, 36 | 2022-02-15 | criteria provided, single submitter | clinical testing |