Submissions for variant NM_006258.4(PRKG1):c.1963-19dup

dbSNP: rs145115489

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000611624	SCV000728267	likely benign	not specified	2018-03-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000611624	SCV005205361	benign	not specified	2024-06-04	criteria provided, single submitter	clinical testing	Variant summary: PRKG1 c.1963-19dupA alters a conserved nucleotide located at a position not widely known to affect splicing. 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 0.00019 in 236416 control chromosomes. The observed variant frequency is approximately 15.57 fold of the estimated maximal expected allele frequency for a pathogenic variant in PRKG1 causing Thoracic Aortic Aneurysms And Dissections phenotype (1.3e-05). To our knowledge, no occurrence of c.1963-19dupA in individuals affected with Thoracic Aortic Aneurysms And Dissections and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 515974). Based on the evidence outlined above, the variant was classified as benign.