Submissions for variant NM_005159.5(ACTC1):c.809-14del

dbSNP: rs1891700511

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175554	SCV001339179	uncertain significance	not specified	2020-03-23	criteria provided, single submitter	clinical testing	Variant summary: ACTC1 c.809-14delT 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 was absent in 106928 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.809-14delT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. At least one co-occurrence with another pathogenic variant has been internally reported (MYBPC3 c.1624+4A>), providing supporting evidence for a benign role. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.