Submissions for variant NM_016203.4(PRKAG2):c.341C>T (p.Pro114Leu)

dbSNP: rs375174733

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001165164	SCV001327337	uncertain significance	Hypertrophic cardiomyopathy 6	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001165165	SCV001327338	uncertain significance	Wolff-Parkinson-White pattern	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color Diagnostics, LLC DBA Color Health	RCV001175845	SCV001339621	uncertain significance	Cardiomyopathy	2023-01-18	criteria provided, single submitter	clinical testing	This variant is located in the PRKAG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 8/282572 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx	RCV001546980	SCV001766596	uncertain significance	not provided	2021-11-24	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 912141; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001175845	SCV002043491	uncertain significance	Cardiomyopathy	2019-05-21	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002032515	SCV002213234	likely benign	Lethal congenital glycogen storage disease of heart	2024-12-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002451346	SCV002614456	uncertain significance	Cardiovascular phenotype	2024-10-07	criteria provided, single submitter	clinical testing	The c.341C>T (p.P114L) alteration is located in exon 3 (coding exon 3) of the PRKAG2 gene. This alteration results from a C to T substitution at nucleotide position 341, causing the proline (P) at amino acid position 114 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002491475	SCV002800700	uncertain significance	Lethal congenital glycogen storage disease of heart; Hypertrophic cardiomyopathy 6; Wolff-Parkinson-White pattern	2021-09-03	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004000267	SCV004842310	uncertain significance	Hypertrophic cardiomyopathy	2024-03-24	criteria provided, single submitter	clinical testing	This variant is located in the PRKAG2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 8/282572 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.