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

gnomAD frequency: 0.00092  dbSNP: rs150797476

Total submissions: 15

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, Mass General Brigham 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	RCV000589664	SCV000235723	likely benign	not provided	2021-03-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22337857, 19525294, 23861362, 24503780, 23299917)
Invitae	RCV001079945	SCV000289969	likely benign	ANKRD1-related dilated cardiomyopathy	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000249347	SCV000318813	likely benign	Cardiovascular phenotype	2018-02-22	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.
Eurofins Ntd Llc (ga)	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 Laboratory Services, 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
CeGaT Center for Human Genetics Tuebingen	RCV000589664	SCV004127064	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	ANKRD1: BP4, BS1
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.
Clinical Genetics, Academic Medical Center	RCV000038846	SCV001924156	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000589664	SCV001929212	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038846	SCV001960075	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000589664	SCV001972883	likely benign	not provided		no assertion criteria provided	clinical testing