Submissions for variant NM_005751.5(AKAP9):c.80C>T (p.Ser27Leu)

gnomAD frequency: 0.00137  dbSNP: rs142401936

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171712	SCV000050732	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000123591	SCV000166930	benign	not specified	2013-02-15	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000624947	SCV000602460	benign	Long QT syndrome 11	2021-11-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618431	SCV000735921	likely benign	Cardiovascular phenotype	2018-08-06	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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000624947	SCV000743169	likely benign	Long QT syndrome 11	2017-03-14	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000624947	SCV000744222	likely benign	Long QT syndrome 11	2016-09-21	criteria provided, single submitter	clinical testing
Invitae	RCV001080217	SCV000752848	likely benign	Long QT syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000171712	SCV000987596	likely benign	not provided		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000123591	SCV001337794	benign	not specified	2020-01-20	criteria provided, single submitter	clinical testing	Variant summary: AKAP9 c.80C>T (p.Ser27Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 249848 control chromosomes in the gnomAD database, including 2 homozygotes. The observed variant frequency is approximately 173 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. Five 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	RCV000624947	SCV002524806	benign	Long QT syndrome 11	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000171712	SCV002586177	benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	AKAP9: BS1, BS2
Fulgent Genetics, Fulgent Genetics	RCV000624947	SCV002810648	benign	Long QT syndrome 11	2021-08-18	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000123591	SCV001925921	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000123591	SCV001952253	benign	not specified		no assertion criteria provided	clinical testing