Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001046418 | SCV001210322 | pathogenic | Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 470 of the BAG3 protein (p.Pro470Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with myofibrillar myopathy (PMID: 30559338, 32859500). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 843736). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BAG3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects BAG3 function (PMID: 30559338). For these reasons, this variant has been classified as Pathogenic. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003339442 | SCV004047862 | pathogenic | Myofibrillar myopathy 6 | criteria provided, single submitter | clinical testing | The missense variant c.1408C>T (p.Pro470Ser) in BAG3 gene has been observed in individual(s) with myofibrillar myopathy (MeisterBroekema M at al.). Experimental studies have shown that this missense affect BAG3 protein function (Meister-Broekema M at al.).The p.Pro470Ser variant is novel (not in any individuals) in gnomAD exomes and 1000 Genomes. The amino acid Pro at position 470 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. This variant has been reported to the ClinVar database as Likely Pathogenic. The amino acid change p.Pro470Ser in BAG3 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. |