Submissions for variant NM_014391.3(ANKRD1):c.196C>G (p.Arg66Gly)

dbSNP: rs397517249

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038845	SCV000062523	benign	not specified	2019-01-22	criteria provided, single submitter	clinical testing	The p.arg66Gly variant in ANKRD1 is classified as benign because it has been identified in 0.1% (307/30616) of South Asian chromosomes and 5 homozygotes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1.
GeneDx	RCV000038845	SCV000518123	benign	not specified	2016-03-25	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	RCV001087075	SCV000658933	benign	ANKRD1-related dilated cardiomyopathy	2024-01-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588271	SCV000699374	likely benign	not provided	2017-08-01	criteria provided, single submitter	clinical testing	Variant summary: The ANKRD1 c.196C>G (p.Arg66Gly) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 173/121398 control chromosomes (3 homozygotes) from ExAC, predominantly observed in the South Asian subpopulation at a frequency of 0.010296 (170/16512). This frequency is about 300 times the estimated maximal expected allele frequency of a pathogenic ANKRD1 variant (0.0000344), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. One clinical diagnostic laboratory has recently classified as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. It has not been found in cohorts of HCM and DCM patients tested at OMGL and LMM centers (Cardio db). Taken together, this variant is currently classified as likely benign.
Ambry Genetics	RCV000621700	SCV000739940	benign	Cardiovascular phenotype	2019-03-18	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	RCV001105938	SCV001262962	likely benign	Primary dilated cardiomyopathy	2018-03-06	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Clinical Genetics, Academic Medical Center	RCV000038845	SCV001917749	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000038845	SCV001974979	benign	not specified		no assertion criteria provided	clinical testing