ClinVar Miner

Submissions for variant NM_004281.4(BAG3):c.1411G>A (p.Glu471Lys)

gnomAD frequency: 0.00002  dbSNP: rs778496291
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617828 SCV000737275 uncertain significance Cardiovascular phenotype 2024-06-21 criteria provided, single submitter clinical testing The p.E471K variant (also known as c.1411G>A), located in coding exon 4 of the BAG3 gene, results from a G to A substitution at nucleotide position 1411. The glutamic acid at codon 471 is replaced by lysine, an amino acid with similar properties. This variant was reported in a BAG3 study cohort, and in a dilated cardiomyopathy cohort however, clinical details were limited (Domínguez F et al. J Am Coll Cardiol, 2018 11;72:2471-2481; Boen HM. Cardiooncology. 2024 Apr;10(1):26). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000686010 SCV000813513 uncertain significance Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH 2024-11-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 471 of the BAG3 protein (p.Glu471Lys). This variant is present in population databases (rs778496291, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with BAG3-related conditions. ClinVar contains an entry for this variant (Variation ID: 519166). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt BAG3 protein function with a positive predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV000686010 SCV002796411 uncertain significance Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH 2022-02-15 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003144397 SCV003829740 uncertain significance not provided 2020-01-23 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000617828 SCV006066938 likely pathogenic Cardiovascular phenotype 2022-12-13 criteria provided, single submitter clinical testing

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