Submissions for variant NM_005159.5(ACTC1):c.129+18dup

dbSNP: rs148433308

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	RCV000253427	SCV000051939	benign	not specified	2023-08-21	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.129+23dupC is located at a position not widely known to affect splicing. 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 0.0059 in 236080 control chromosomes, predominantly at a frequency of 0.09 within the African or African-American subpopulation in the gnomAD database, including 64 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is significantly higher than the estimated maximal expected allele frequency for a pathogenic variant in ACTC1 causing Hypertrophic Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.129+23dupC in individuals affected with Hypertrophic Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000253427	SCV000310857	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV001529870	SCV001896313	benign	not provided	2015-05-29	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529870	SCV001744075	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000253427	SCV001955679	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000253427	SCV001970088	benign	not specified		no assertion criteria provided	clinical testing