ClinVar Miner

Submissions for variant NM_005751.4(AKAP9):c.510G>C (p.Glu170Asp) (rs144888041)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000170646 SCV000050735 likely benign not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000170646 SCV000223198 uncertain significance not provided 2012-02-23 criteria provided, single submitter clinical testing p.E170D:GAG>GAC at the protein level, c.510 G>C at the DNA level. A heterozygous G>C nucleotide substitution was identified in exon 6 of the AKAP9 gene, resulting in replacement of the normal Glutamic acid codon (GAG) with an Aspartic acid codon (GAC) at amino acid position 170 in the A-kinase anchor protein 9. This missense change is denoted Glu170Asp (aka E170D) at the protein level and c.510 G>C at the cDNA level. The Glu170Asp variant in the AKAP9 gene has not been previously reported as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The Glu170Asp variant was not detected in 600 alleles from control individuals of Caucasian and African American ancestry tested at GeneDx, indicating it is not a common benign variant in these populations. However, Glu170Asp results in a conservative substitution of a negatively charged amino acid with another at a position that is not highly conserved across species. In addition, no missense mutations have been reported in nearby codons of the AKAP9 gene, and Glu170Asp does not occur in or near either of the two known binding sites of AKAP9, indicating this region of the protein may be tolerant of change. With the molecular and clinical information available, we cannot determine the clinical significance of Glu170Asp and classify it as a variant of unknown clinical significance at this time. The variant is found in LQT panel(s).
Invitae RCV000197421 SCV000253473 benign Long QT syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000242948 SCV000318720 likely benign Cardiovascular phenotype 2018-11-09 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Illumina Clinical Services Laboratory,Illumina RCV000354957 SCV000470198 uncertain significance Romano-Ward syndrome 2016-06-14 criteria provided, single submitter clinical testing
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000584786 SCV000692522 benign Brugada syndrome 1 2017-03-16 criteria provided, single submitter research The AKAP9 Glu170Asp has been previously identified in a Marfan Syndrome case, the patient also carried a FBN1 Cys2592Arg variant (Garzon SS, 2015). The AKAP9 Glu170Asp variant is found at high frequency in the Exome Aggregation Consortium dataset (MAF= 0.002;, suggesting that it is a common polymorphism (Ng D, et al., 2013). We identified this variant in one proband with Brugada syndrome, who has no family history of disease or SCD. The proband also carries a rare variant (RYR2 Asp1412Gly). Furthermore, computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to be well tolerated. Based on a high allele frequency in the general population and in silico tools predicting no deleterious affect on the protein, we classify this variant as "benign".
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000624949 SCV000743171 likely benign Long QT syndrome 11 2016-12-13 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000170646 SCV000883381 benign not provided 2017-09-29 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000853011 SCV000995767 likely benign Catecholaminergic polymorphic ventricular tachycardia 2017-12-18 criteria provided, single submitter clinical testing

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