ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.129+19_129+20insT

gnomAD frequency: 0.00001  dbSNP: rs386134228
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001698944 SCV000051938 benign not specified 2023-05-04 criteria provided, single submitter clinical testing Variant summary: ACTC1 c.129+19_129+20insT 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 0.0012 in 237926 control chromosomes (gnomAD), predominantly at a frequency of 0.0094 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 376 fold of 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 South Asian origin. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV001530117 SCV000207701 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Invitae RCV002054477 SCV002402819 benign Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2024-01-29 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001530117 SCV001744770 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001698944 SCV001924006 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001698944 SCV001970398 benign not specified no assertion criteria provided clinical testing

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