Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002007521 | SCV002228001 | pathogenic | Lethal congenital glycogen storage disease of heart | 2021-06-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Val336 amino acid residue in PRKAG2. Other variant(s) that disrupt this residue have been observed in individuals with PRKAG2-related conditions (PMID: 28546535), which suggests that this may be a clinically significant amino acid residue. This sequence change replaces valine with alanine at codon 336 of the PRKAG2 protein (p.Val336Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 28431061; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. 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 tolerated. |