ClinVar Miner

Submissions for variant NM_001103.3(ACTN2):c.506G>C (p.Arg169Thr) (rs727505146)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788413 SCV000927512 uncertain significance not provided 2018-01-09 criteria provided, single submitter clinical testing
Invitae RCV000702566 SCV000831424 uncertain significance Dilated cardiomyopathy 1AA; Primary familial hypertrophic cardiomyopathy 2018-04-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 169 of the ACTN2 protein (p.Arg169Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ACTN2-related disease. ClinVar contains an entry for this variant (Variation ID: 179815). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156614 SCV000206335 uncertain significance not specified 2014-07-03 criteria provided, single submitter clinical testing The Arg169Thr variant in ACTN2 has not been previously reported in individuals w ith cardiomyopathy or in large population studies. Computational prediction tool s and conservation analysis do not provide strong support for or against an impa ct to the protein. In summary, the clinical significance of the Arg169Thr varian t is uncertain.

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