Submissions for variant NM_005159.5(ACTC1):c.809-58TG[22]

dbSNP: rs59431308

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000404767	SCV000390673	uncertain significance	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000299457	SCV000390674	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000356365	SCV000390675	uncertain significance	Atrial septal defect	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000264159	SCV000390676	uncertain significance	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000302922	SCV000390677	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001264605	SCV001442837	benign	not specified	2020-10-26	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.809-14_809-13delTG is located to a polymorphic region, occurring in a poly-GT tract in intron 5, close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.063 in 132330 control chromosomes in the gnomAD database (v3, genomes dataset), including 296 homozygotes. The observed variant frequency is approximately 2500-fold of the estimated maximal expected allele frequency for a pathogenic variant in ACTC1 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.809-14_809-13delTG in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002061177	SCV002462357	likely benign	Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5	2025-02-04	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701847	SCV001929506	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001264605	SCV001952709	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003972346	SCV004799246	likely benign	ACTC1-related disorder	2021-04-01	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).