ClinVar Miner

Submissions for variant NM_004281.4(BAG3):c.872C>T (p.Ser291Leu)

gnomAD frequency: 0.00005  dbSNP: rs368866313
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037902 SCV000061564 uncertain significance not specified 2013-03-04 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ser291Leu varia nt in BAG3 has not been reported in the literature nor previously identified by our laboratory. This variant has been identified in 3/8600 European American chr omosomes from a broad population by the NHLBI Exome Sequencing Project (http://e vs.gs.washington.edu/EVS). Serine (Ser) at position 291 is not conserved in mamm als and one species (rock hyrax) carries a leucine (Leu; this variant), raising the possibility that this change may be tolerated. In addition, other computatio nal analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) suggest that this variant may not impact the protein, though this information i s not predictive enough to rule out pathogenicity. Although this data supports t hat the Ser291Leu variant may be benign, additional studies are needed to fully assess its clinical significance.
Eurofins Ntd Llc (ga) RCV000726747 SCV000702729 uncertain significance not provided 2016-11-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000822800 SCV000963617 likely benign Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH 2025-01-28 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002470734 SCV002767646 likely benign Dilated cardiomyopathy 1HH 2022-09-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Likely Benign. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from serine to leucine (exon 3). (N) 0251 - Variant is heterozygous. (N) 0308 - Population frequency for this variant is out of keeping with known incidence of myofibrillar myopathy. (B) 0504 - Same amino acid change has been observed in mammals. (B) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant has previously been described as variant of uncertain significance in multiple indivudials (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Fulgent Genetics, Fulgent Genetics RCV000822800 SCV002775282 uncertain significance Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH 2022-01-26 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000726747 SCV003829738 uncertain significance not provided 2021-10-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV004018853 SCV004912461 uncertain significance Cardiovascular phenotype 2020-06-29 criteria provided, single submitter clinical testing The c.872C>T (p.S291L) alteration is located in exon 3 (coding exon 3) of the BAG3 gene. This alteration results from a C to T substitution at nucleotide position 872, causing the serine (S) at amino acid position 291 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000726747 SCV005326852 uncertain significance not provided 2023-12-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.