Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000230623 | SCV000290200 | likely pathogenic | Lethal congenital glycogen storage disease of heart | 2022-10-13 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.His401 amino acid residue in PRKAG2. Other variant(s) that disrupt this residue have been observed in individuals with PRKAG2-related conditions (PMID: 32215636), which suggests that this may be a clinically significant amino acid residue. ClinVar contains an entry for this variant (Variation ID: 241091). This missense change has been observed in individuals with PRKAG2-related conditions (PMID: 32259713). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 401 of the PRKAG2 protein (p.His401Asp). |