ClinVar Miner

Submissions for variant NM_014391.3(ANKRD1):c.197G>A (p.Arg66Gln) (rs150797476)

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Total submissions: 10
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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 RCV000172518 SCV000050888 likely benign Primary dilated cardiomyopathy 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038846 SCV000062524 uncertain significance not specified 2015-05-19 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000038846 SCV000235723 likely benign not specified 2017-07-25 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.
Invitae RCV001079945 SCV000289969 likely benign ANKRD1-related dilated cardiomyopathy 2020-10-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000249347 SCV000318813 likely benign Cardiovascular phenotype 2018-02-22 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000589664 SCV000331401 uncertain significance not provided 2015-07-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589664 SCV000699375 likely benign not provided 2017-07-31 criteria provided, single submitter clinical testing Variant summary: The ANKRD1 c.197G>A (p.Arg66Gln) variant involves the alteration of a non-conserved nucleotide, resulting in a missense change in the ankyrin repeat-containing domain (InterPro). 4/5 in silico tools predict benign outcome for this variant. This variant was found in 116/122204 control chromosomes (ExAC) at a frequency of 0.0009492, which is approximately 28 times the estimated maximal expected allele frequency of a pathogenic ANKRD1 variant (0.0000344), suggesting this variant is likely a benign polymorphism. In gnomAD, the variants allele frequency is 0.001079 (299/ 277022 chromosomes). This variant has been reported in one case who had family history of premature sudden deaths in first-degree relatives (Duboscq-Bidot_EJH_2009). Functional analysis in the same study showed a non-significant, mild effect on transcriptional repression was observed as well as a non-significant increase in cell area in cardiomyocytes, suggesting protein function is not significantly impacted by the variant. In ClinVar, while four clinical labs have classified it as uncertain significance, three have classified it as likely benign. Taken together, based on its allele frequency in general population and the possibility that it is likely to be a functional polymorphism rather than causal variant, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000172518 SCV001262961 uncertain significance Primary dilated cardiomyopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170404 SCV001332981 benign Cardiomyopathy 2018-04-25 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000589664 SCV001423453 not provided not provided no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 01-06-2017 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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