Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000457488 | SCV000551580 | uncertain significance | Lethal congenital glycogen storage disease of heart | 2016-06-09 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PRKAG2-related disease. This sequence change replaces lysine with isoleucine at codon 11 of the PRKAG2 protein (p.Lys11Ile). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and isoleucine. |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000786199 | SCV000924910 | uncertain significance | not provided | 2016-10-18 | no assertion criteria provided | provider interpretation | p.Lys11Ile (c.32A>T) in the PRKAG2 gene (NM_016203.3) The lab classifies this variant as a variant of unknown significance. Given a lack of case data, we consider this variant a variant of unknown significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). We do recommend testing for this variant in family members that also have cardiomyopathy. There is no case data. In silico analysis with PolyPhen-2 predicts the variant to be benign. The Lys at codon 11 is weakly conserved across species. No other variants have been reported in association with disease at this codon and nearby codons. This variant falls outside of a known functional domain. There is no variation at codon 11 listed in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of October 18, 2016). The average coverage at that site in ExAC is 30x. |