ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.991G>A (p.Ala331Thr) (rs749520121)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000222006 SCV000271914 likely benign not specified 2017-11-17 criteria provided, single submitter clinical testing p.Ala331Thr in exon 10 of LDB3: This variant is not expected to have clinical si gnificance because it was detected in an unaffected parent of an individual with early onset DCM, and an alternate genetic explanation for the disease was ident ified. In addition, computational prediction tools and conservation analysis sug gest that the p.Ala331Thr variant may not impact the protein. The variant was al so identified in 0.02% (2/10126) of Ashkenazi Jewish and 5/125880 European chrom osomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute. org; dbSNP rs749520121). ACMG/AMP Criteria applied: BS2, BP4, BP5.
GeneDx RCV000766999 SCV000491740 uncertain significance not provided 2016-11-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the LDB3 gene. Although the A331T variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge, it has been classified as a variant of uncertain significance by one other clinical laboratory in ClinVar (Landrum et al., 2016; SCV000271914.1). The A331T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or with any significant frequency in the ExAC data set. The A331T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is not conserved. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Ambry Genetics RCV000620055 SCV000735484 likely benign Cardiovascular phenotype 2019-03-28 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Invitae RCV001345092 SCV001539191 uncertain significance Myofibrillar myopathy, ZASP-related 2020-08-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 331 of the LDB3 protein (p.Ala331Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between the two amino acids. The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*7251G>A in the primary transcript. This variant is present in population databases (rs749520121, ExAC 0.003%). This variant has not been reported in the literature in individuals with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 228797). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000766999 SCV001716078 uncertain significance not provided 2021-03-10 criteria provided, single submitter clinical testing

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.