ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1016C>G (p.Ala339Gly)

gnomAD frequency: 0.00001  dbSNP: rs764530865
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
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 RCV000217551 SCV000271907 uncertain significance not specified 2017-08-04 criteria provided, single submitter clinical testing The p.Ala339Gly variant in LDB3 has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/15204 African chromosomes by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Compu tational prediction tools and conservation analysis suggest that this variant ma y not impact the protein, though this information is not predictive enough to ru le out pathogenicity. In summary, the clinical significance of the p.Ala339Gly v ariant is uncertain.
Ambry Genetics RCV002338681 SCV002640470 uncertain significance Cardiovascular phenotype 2022-10-03 criteria provided, single submitter clinical testing The p.A339G variant (also known as c.1016C>G), located in coding exon 7 of the LDB3 gene, results from a C to G substitution at nucleotide position 1016. The alanine at codon 339 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a subject with hypertrophic cardiomyopathy (HCM) (Burstein DS et al. Pediatr Res, 2021 05;89:1470-1476). This amino acid position is 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.
Invitae RCV003114382 SCV003787459 uncertain significance Myofibrillar myopathy 4 2021-12-24 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 228792). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 32746448). This variant is present in population databases (rs764530865, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 339 of the LDB3 protein (p.Ala339Gly). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*7276C>G in the primary transcript.

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.