Submissions for variant NM_014391.3(ANKRD1):c.827C>T (p.Ala276Val)

gnomAD frequency: 0.00244  dbSNP: rs35550482

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172739	SCV000051363	benign	Primary dilated cardiomyopathy	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038857	SCV000062535	benign	not specified	2018-08-29	criteria provided, single submitter	clinical testing	The p.Ala276Val variant in ANKRD1 is classified as benign because it has been de tected in 2% (212/10136) of Ashkenazi Jewish chromosomes by gnomAD (http://gnoma d.broadinstitute.org). ACMG/AMP Criteria applied: BA1.
Eurofins Ntd Llc (ga)	RCV000038857	SCV000232725	likely benign	not specified	2015-05-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000038857	SCV000235727	benign	not specified	2018-03-06	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.
Ambry Genetics	RCV000252792	SCV000318911	benign	Cardiovascular phenotype	2017-02-23	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Invitae	RCV001081125	SCV000563271	benign	ANKRD1-related dilated cardiomyopathy	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590657	SCV000699381	likely benign	not provided	2017-07-31	criteria provided, single submitter	clinical testing	Variant summary: The ANKRD1 c.827C>T (p.Ala276Val) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). In vitro functional analysis shows that this variant leads to decrease in transcriptional repression activity (Duboscq-Bidot_2009).This variant was found in 346/121722 control chromosomes (1 homozygote) including ExAC at a frequency of 0.0028425, which is approximately 83 times the estimated maximal expected allele frequency of a pathogenic ANKRD1 variant (0.0000344), suggesting this variant is likely a benign polymorphism. This variant has been reported in two siblings with DCM without strong evidence for causality (Duboscq-Bidot_2009). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign. Taken together, this variant is currently classified as likely benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000623947	SCV000740548	likely benign	Primary familial hypertrophic cardiomyopathy	2017-05-23	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000614830	SCV000743701	likely benign	Congenital total pulmonary venous return anomaly	2016-10-19	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000614830	SCV000745109	uncertain significance	Congenital total pulmonary venous return anomaly	2015-09-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770301	SCV000901734	likely benign	Cardiomyopathy	2019-04-30	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852623	SCV000995327	benign	Cardiomyopathy; Systolic heart failure	2019-04-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000172739	SCV001259573	likely benign	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590657	SCV001471588	benign	not provided	2023-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590657	SCV004127063	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	ANKRD1: BP4, BS2
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000614830	SCV000732967	benign	Congenital total pulmonary venous return anomaly		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038857	SCV001924780	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038857	SCV001952265	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000590657	SCV001974746	likely benign	not provided		no assertion criteria provided	clinical testing