Submissions for variant NM_004281.4(BAG3):c.583A>G (p.Ser195Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003784651	SCV004575675	uncertain significance	Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH	2023-04-16	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs528288616, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 195 of the BAG3 protein (p.Ser195Gly). This variant has not been reported in the literature in individuals affected with BAG3-related conditions. 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. 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 not expected to disrupt BAG3 protein function.
Ambry Genetics	RCV004992831	SCV005543972	uncertain significance	Cardiovascular phenotype	2024-10-04	criteria provided, single submitter	clinical testing	The c.583A>G (p.S195G) alteration is located in exon 3 (coding exon 3) of the BAG3 gene. This alteration results from a A to G substitution at nucleotide position 583, causing the serine (S) at amino acid position 195 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.