Submissions for variant NM_006258.4(PRKG1):c.1071A>G (p.Lys357=)

gnomAD frequency: 0.00097  dbSNP: rs75650199

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001002192	SCV000289503	benign	Aortic aneurysm, familial thoracic 8	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002311069	SCV000319796	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-06-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001580043	SCV000532845	likely benign	not provided	2021-08-02	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660232	SCV000782235	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001002192	SCV001160064	benign	Aortic aneurysm, familial thoracic 8	2023-09-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001580043	SCV004125369	benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	PRKG1: BS1, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479074	SCV004223190	benign	not specified	2023-11-27	criteria provided, single submitter	clinical testing	Variant summary: PRKG1 c.1071A>G alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00084 in 249390 control chromosomes. The observed variant frequency is approximately 67.043 fold of the estimated maximal expected allele frequency for a pathogenic variant in PRKG1 causing Thoracic Aortic Aneurysms And Dissections phenotype (1.3e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1071A>G in individuals affected with Thoracic Aortic Aneurysms And Dissections and no experimental evidence demonstrating its impact on protein function have been reported. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV002311069	SCV004239618	benign	Familial thoracic aortic aneurysm and aortic dissection	2023-01-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003977674	SCV004797890	likely benign	PRKG1-related disorder	2021-09-15	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580043	SCV001809466	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001580043	SCV001929373	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001580043	SCV001966768	likely benign	not provided		no assertion criteria provided	clinical testing