ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.850A>T (p.Ile284Phe) (rs397517073)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038341 SCV000062013 uncertain significance not specified 2014-05-15 criteria provided, single submitter clinical testing The Ile284Phe variant in ACTC1 has not been previously reported in individuals w ith cardiomyopathy and was absent from large population studies. This variant ha s been identified by our laboratory in 1 African American infant with HCM (who c arried a variant of uncertain significance in another gene) and was found to seg regate with disease in an affected sibling (who did not carry the other variant) . Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical signi ficance of the Ile284Phe variant is uncertain.
Invitae RCV000808186 SCV000948282 uncertain significance Familial hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2018-09-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with phenylalanine at codon 284 of the ACTC1 protein (p.Ile284Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 45191). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000853444 SCV000996355 uncertain significance Bicuspid aortic valve 2017-12-13 criteria provided, single submitter research

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