Submissions for variant NM_005751.5(AKAP9):c.2425A>G (p.Ile809Val)

gnomAD frequency: 0.00298  dbSNP: rs144615758

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000170633	SCV000050731	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000185482	SCV000223185	likely benign	not specified	2016-10-25	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	RCV001086739	SCV000563318	benign	Long QT syndrome	2024-01-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620147	SCV000737528	likely benign	Cardiovascular phenotype	2018-12-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000185482	SCV001519468	benign	not specified	2021-03-15	criteria provided, single submitter	clinical testing	Variant summary: AKAP9 c.2425A>G (p.Ile809Val) 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 0.00061 in 250678 control chromosomes, predominantly at a frequency of 0.0088 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2640-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 a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.2425A>G in individuals affected with Long QT Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV002253257	SCV002524821	benign	Long QT syndrome 11	2021-12-05	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002253257	SCV002794856	likely benign	Long QT syndrome 11	2021-08-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003947450	SCV004765136	benign	AKAP9-related disorder	2019-10-28	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).