ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.1092C>T (p.Tyr364=) (rs140261885)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038320 SCV000061989 likely benign not specified 2015-07-02 criteria provided, single submitter clinical testing p.Tyr364Tyr in exon 7 of ACTC1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 3/10406 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs140261885).
GeneDx RCV000038320 SCV000520896 likely benign not specified 2016-08-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000038320 SCV000916414 benign not specified 2018-07-09 criteria provided, single submitter clinical testing Variant summary: ACTC1 c.1092C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within African control individuals in the gnomAD database is approximately 17-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 a benign polymorphism found primarily in populations of African origin. The variant, c.1092C>T, has been reported in the literature in individuals affected with Cardiomyopathy but also in controls and were classified as 'polymorphisms' (Tesson_2000, Takai_1999). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two 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.
Invitae RCV000866658 SCV001007784 likely benign Familial hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2019-12-31 criteria provided, single submitter clinical testing
Color RCV001183727 SCV001349537 likely benign Cardiomyopathy 2019-02-16 criteria provided, single submitter clinical testing

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