Submissions for variant NM_004281.4(BAG3):c.1651C>A (p.Gln551Lys)

gnomAD frequency: 0.00001  dbSNP: rs577455773

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV001002800	SCV001160773	uncertain significance	Dilated cardiomyopathy 1HH	2019-09-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002391073	SCV002703484	uncertain significance	Cardiovascular phenotype	2019-09-18	criteria provided, single submitter	clinical testing	The p.Q551K variant (also known as c.1651C>A), located in coding exon 4 of the BAG3 gene, results from a C to A substitution at nucleotide position 1651. The glutamine at codon 551 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005209530	SCV005850534	uncertain significance	Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH	2024-09-08	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 551 of the BAG3 protein (p.Gln551Lys). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 812168). 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 not expected to disrupt BAG3 protein function with a negative 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.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001724207	SCV001951191	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001724207	SCV001966284	likely benign	not provided		no assertion criteria provided	clinical testing