Submissions for variant NM_005751.5(AKAP9):c.3827G>A (p.Arg1276Gln)

gnomAD frequency: 0.00635  dbSNP: rs146797353

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171779	SCV000050788	benign	not specified	2013-06-24	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228352	SCV000289089	benign	Long QT syndrome	2025-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245265	SCV000317507	benign	Cardiovascular phenotype	2015-04-23	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.
Eurofins Ntd Llc (ga)	RCV000171779	SCV000331373	benign	not specified	2016-08-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000278007	SCV000470239	likely benign	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000171779	SCV001437411	benign	not specified	2020-09-08	criteria provided, single submitter	clinical testing	Variant summary: AKAP9 c.3827G>A (p.Arg1276Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0093 in 220076 control chromosomes in the gnomAD database, including 21 homozygotes. The observed variant frequency is approximately 2790 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. 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	RCV001706111	SCV001867385	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30821013, 29177109, 26230511)
Genome-Nilou Lab	RCV002253266	SCV002524831	benign	Long QT syndrome 11	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001706111	SCV003917166	benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	AKAP9: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001706111	SCV005220982	likely benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000171779	SCV001920980	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000171779	SCV001956548	benign	not specified		no assertion criteria provided	clinical testing