Submissions for variant NM_005751.5(AKAP9):c.4841G>A (p.Arg1614Gln)

gnomAD frequency: 0.00849  dbSNP: rs2230768

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000123575	SCV000050794	benign	not specified	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000123575	SCV000166914	benign	not specified	2012-05-18	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206847	SCV000259245	benign	Long QT syndrome	2025-02-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251706	SCV000318513	benign	Cardiovascular phenotype	2016-09-23	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.
Illumina Laboratory Services, Illumina	RCV000356670	SCV000470258	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	RCV000123575	SCV001821492	benign	not specified	2021-08-09	criteria provided, single submitter	clinical testing	Variant summary: AKAP9 c.4841G>A (p.Arg1614Gln) 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 0.0019 in 251238 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 558 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. To our knowledge, no occurrence of c.4841G>A in individuals affected with Long QT Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three 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.
Genome-Nilou Lab	RCV002253223	SCV002524842	benign	Long QT syndrome 11	2021-12-05	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002253223	SCV002803062	benign	Long QT syndrome 11	2021-07-21	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004704965	SCV005220988	likely benign	not provided		criteria provided, single submitter	not provided