Submissions for variant NM_005159.5(ACTC1):c.617-7T>C

gnomAD frequency: 0.00001  dbSNP: rs750536667

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000774048	SCV000907748	likely benign	Cardiomyopathy	2018-09-29	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000774048	SCV001333936	likely benign	Cardiomyopathy	2020-05-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001459888	SCV001663743	likely benign	Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5	2024-01-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002233787	SCV002511706	benign	not specified	2022-04-05	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.617-7T>C 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 4e-05 in 251460 control chromosomes. The observed variant frequency is approximately 2 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. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
All of Us Research Program, National Institutes of Health	RCV004001344	SCV004828753	likely benign	Hypertrophic cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001729701	SCV001978387	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001729701	SCV001979405	likely benign	not provided		no assertion criteria provided	clinical testing