Submissions for variant NM_005159.5(ACTC1):c.809-58TG[21]

dbSNP: rs59431308

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000328860	SCV000390683	likely benign	Atrial septal defect	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000362302	SCV000390684	likely benign	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000293852	SCV000390685	likely benign	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307785	SCV000390686	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000304122	SCV000390687	likely benign	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000328860	SCV000390693	uncertain significance	Atrial septal defect	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307785	SCV000390694	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000362302	SCV000390695	uncertain significance	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000293852	SCV000390696	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000304122	SCV000390697	uncertain significance	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001712023	SCV000730638	benign	not provided	2018-06-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000607885	SCV001363390	benign	not specified	2019-08-12	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.809-16_809-13delTGTG 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 allele was found at a frequency of 0.14 in 24922 control chromosomes in the gnomAD database, including 309 homozygotes. The observed variant frequency is approximately 5446-folds over 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. Two ClinVar submissions (evaluation after 2014) cite the variant once as benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002061178	SCV002378394	likely benign	Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004017590	SCV004849291	uncertain significance	Cardiovascular phenotype	2015-11-16	criteria provided, single submitter	clinical testing	The c.809-16_809-13delTGTG alteration is located in Intron 5 (E) of the ACTC1 gene. This alteration consists of a deletion of 4 nucleotides at nucleotide position c.809-16 Intron 5 (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000607885	SCV001932512	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000607885	SCV001951539	benign	not specified		no assertion criteria provided	clinical testing