Submissions for variant NM_005159.5(ACTC1):c.809-58TG[24]

dbSNP: rs59431308

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000323142	SCV000390663	uncertain significance	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000380146	SCV000390664	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000288512	SCV000390665	uncertain significance	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000330574	SCV000390666	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000383960	SCV000390667	uncertain significance	Atrial septal defect	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000323142	SCV000390703	uncertain significance	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000380146	SCV000390704	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000288512	SCV000390705	uncertain significance	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000330574	SCV000390706	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000383960	SCV000390707	uncertain significance	Atrial septal defect	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192735	SCV001361037	benign	not specified	2019-11-05	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.809-14_809-13dupTG alters a non-conserved nucleotide located 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 0.13 in 24922 control chromosomes in the gnomAD database, including 285 homozygotes. The observed variant frequency is well above 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_809-13dupTG in individuals affected with Cardiomyopathy and no experimental evidence demonstrating an impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (TTR c.424G>A, p.Val142Ile; internal sample), providing supporting evidence for a benign role. One ClinVar submitter (evaluation after 2014) cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001528900	SCV001891536	benign	not provided	2019-08-06	criteria provided, single submitter	clinical testing
Invitae	RCV002056455	SCV002439959	likely benign	Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5	2024-02-01	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528900	SCV001741435	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001192735	SCV001930695	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001192735	SCV001958571	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528900	SCV001976176	likely benign	not provided		no assertion criteria provided	clinical testing