Submissions for variant NM_014391.3(ANKRD1):c.348G>A (p.Thr116=)

gnomAD frequency: 0.00748  dbSNP: rs137914723

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038851	SCV000062529	benign	not specified	2015-07-07	criteria provided, single submitter	clinical testing	p.Thr116Thr in exon 4 of ANKRD1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 11.6% (1317/11318 ) of Latino chromosomes including 90 homozygotes and 1.3% (110/8288) of East Asi an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org/; dbSNP rs137914723).
GeneDx	RCV000038851	SCV000166996	benign	not specified	2013-10-08	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	RCV000234360	SCV000289972	benign	ANKRD1-related dilated cardiomyopathy	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245026	SCV000318795	benign	Cardiovascular phenotype	2015-08-28	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.
Illumina Laboratory Services, Illumina	RCV000313420	SCV000366037	benign	Primary dilated cardiomyopathy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586581	SCV000699379	benign	not provided	2017-07-31	criteria provided, single submitter	clinical testing	Variant summary: The ANKRD1 c.348G>A (p.Thr116Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a polymorphism outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant affects binding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1468/117822 control chromosomes (91 homozygotes) from ExAC, predominantly observed in the Latino subpopulation at a frequency of 0.116363 (1317/11318). This frequency is about 3385 times the estimated maximal expected allele frequency of a pathogenic ANKRD1 variant (0.0000344), thus this is a common benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories (via ClinVar) have classified this variant as benign/likely benign. This variant was also reported as a polymorphism in the literature (Arimura _2009). Taken together, this variant is classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770306	SCV000901739	benign	Cardiomyopathy	2015-11-19	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000586581	SCV001798016	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000038851	SCV001917708	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038851	SCV001952571	benign	not specified		no assertion criteria provided	clinical testing