Submissions for variant NM_005159.5(ACTC1):c.809-58TG[20]

dbSNP: rs59431308

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194107	SCV001363388	benign	not specified	2019-08-13	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.809-18_809-13delTGTGTG 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.809-18_809-13delTGTGTG in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002069247	SCV002480094	likely benign	Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5	2025-02-02	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001194107	SCV001742572	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001194107	SCV001928449	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001194107	SCV001957458	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003918767	SCV004734575	likely benign	ACTC1-related disorder	2021-04-21	no assertion criteria provided	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).