Submissions for variant NM_005751.5(AKAP9):c.8485G>A (p.Glu2829Lys)

gnomAD frequency: 0.00303  dbSNP: rs149946443

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000251850	SCV000318430	benign	Cardiovascular phenotype	2015-07-15	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000439400	SCV000511118	likely benign	not provided	2016-07-22	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Invitae	RCV001081330	SCV000627762	benign	Long QT syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625229	SCV000744223	benign	Long QT syndrome 11	2017-07-13	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000853021	SCV000995778	benign	Restrictive cardiomyopathy	2018-08-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192963	SCV001361456	benign	not specified	2019-09-25	criteria provided, single submitter	clinical testing	Variant summary: AKAP9 c.8485G>A (p.Glu2829Lys) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00064 in 249136 control chromosomes (gnomAD). The observed variant frequency is approximately 64 fold of the estimated maximal expected allele frequency for a pathogenic variant in AKAP9 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. Four 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 benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV000439400	SCV001805016	likely benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000625229	SCV002524865	benign	Long QT syndrome 11	2021-12-05	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000439400	SCV001926068	likely benign	not provided		no assertion criteria provided	clinical testing