Submissions for variant NM_005751.5(AKAP9):c.139C>T (p.His47Tyr)

gnomAD frequency: 0.00775  dbSNP: rs35669569

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171775	SCV000050792	benign	not specified	2013-06-24	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204404	SCV000261484	benign	Long QT syndrome	2025-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000254067	SCV000318648	benign	Cardiovascular phenotype	2015-06-29	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.
Illumina Laboratory Services, Illumina	RCV000407417	SCV000470193	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000624948	SCV000602458	benign	Long QT syndrome 11	2019-03-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000624948	SCV000743170	benign	Long QT syndrome 11	2016-05-11	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000853010	SCV000995766	benign	Atrial fibrillation; Cardiomyopathy; Heart failure; Hypertrophic cardiomyopathy	2019-05-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000171775	SCV001448555	benign	not specified	2020-11-23	criteria provided, single submitter	clinical testing	Variant summary: AKAP9 c.139C>T (p.His47Tyr) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.008 in 251216 control chromosomes in the gnomAD database, including 12 homozygotes. The observed variant frequency is approximately 2413 fold of the estimated maximal expected allele frequency for a pathogenic variant in AKAP9 causing Long QT Syndrome phenotype (3.3e-06), strongly suggesting that the variant is benign. Six 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	RCV001711344	SCV001944416	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000624948	SCV002524808	benign	Long QT syndrome 11	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001711344	SCV004164280	benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	AKAP9: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001711344	SCV005220964	likely benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000171775	SCV001919455	benign	not specified		no assertion criteria provided	clinical testing