Submissions for variant NM_005159.5(ACTC1):c.809-58TG[17]

dbSNP: rs59431308

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000296187	SCV000390688	uncertain significance	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000351039	SCV000390689	uncertain significance	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406995	SCV000390690	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000311286	SCV000390691	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000347484	SCV000390692	uncertain significance	Atrial septal defect	2016-06-14	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852704	SCV000995418	likely benign	Primary dilated cardiomyopathy	2019-06-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194108	SCV001363389	benign	not specified	2019-08-13	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.809-24_809-13delTGTGTGTGTGTG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 106928 control chromosomes (gnomAD). However, the variant is located in a highly polymorphic region within a run of TG dinucleotide tandem repeats. In addition, surrounding variants with variations of TG repeats (expansions and deletions) have been classified as benign. Therefore, suggesting the region is tolerable to expansions and deletions of this dinucleotide sequence. To our knowledge, no occurrence of c.809-24_809-13del12 in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV001859888	SCV002137421	likely benign	Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003910188	SCV004733409	likely benign	ACTC1-related condition	2021-03-01	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).