ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.881G>A (p.Arg294His) (rs151335530)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000429285 SCV000527934 uncertain significance not provided 2018-08-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the BAG3 gene. The R294H variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 9/245668 (0.004%) alleles from individuals of multiple ethnic backgrounds in large population cohorts (Lek et al., 2016). The R294H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Klaassen Lab,Charite University Medicine Berlin RCV000853121 SCV000995832 uncertain significance Primary dilated cardiomyopathy 2019-07-03 criteria provided, single submitter research
Invitae RCV001048342 SCV001212342 uncertain significance Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2019-02-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 294 of the BAG3 protein (p.Arg294His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs151335530, ExAC 0.02%). This variant has not been reported in the literature in individuals with BAG3-related conditions. ClinVar contains an entry for this variant (Variation ID: 386339). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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