Submissions for variant NM_016203.4(PRKAG2):c.477CTC[2] (p.Ser162del)

dbSNP: rs1002236859

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000700427	SCV000829181	uncertain significance	Lethal congenital glycogen storage disease of heart	2021-09-02	criteria provided, single submitter	clinical testing	This variant, c.483_485del, results in the deletion of 1 amino acid(s) of the PRKAG2 protein (p.Ser162del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PRKAG2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
GeneDx	RCV001562897	SCV001785739	uncertain significance	not provided	2019-06-03	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID# 561419; Landrum et al., 2016); Variant results in an in-frame deletion of a single serine residue, denoted p.S162del; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265863	SCV002547489	uncertain significance	not specified	2022-05-24	criteria provided, single submitter	clinical testing	Variant summary: PRKAG2 c.483_485delCTC (p.Ser162del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant was absent in 251414 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.483_485delCTC in individuals affected with Hypertrophic Cardiomyopathy With Wolff-Parkinson-White and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.