ClinVar Miner

Submissions for variant NM_001103.3(ACTN2):c.1822C>T (p.Arg608Trp) (rs397516571)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558013 SCV000636942 uncertain significance Dilated cardiomyopathy 1AA; Primary familial hypertrophic cardiomyopathy 2017-03-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 608 of the ACTN2 protein (p.Arg608Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs397516571, ExAC 0.001%) but has not been reported in the literature in individuals with a ACTN2-related disease. ClinVar contains an entry for this variant (Variation ID: 43916). 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. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036886 SCV000060541 uncertain significance not specified 2012-08-02 criteria provided, single submitter clinical testing The Arg608Trp variant in ACTN2 has not been reported in the literature nor previ ously identified by our laboratory. Computational analyses (biochemical amino ac id properties, conservation, AlignGVGD, PolyPhen2, and SIFT) predict an impact t o the protein but their accuracy is unknown. Additional information is needed to fully assess the clinical significance of this variant.

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