ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.690-4739G>A (rs376489385)

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
Ambry Genetics RCV000618434 SCV000736688 uncertain significance Cardiovascular phenotype 2016-10-20 criteria provided, single submitter clinical testing The p.G145S variant (also known as c.433G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide position 433. The glycine at codon 145 is replaced by serine, an amino acid with similar properties. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/12806) total alleles studied and 0.02% (2/8498) European American alleles. Based on data from ExAC, the A allele has an overall frequency of less than 0.01% (5/105598). This amino acid position is highly 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.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000661930 SCV000784255 uncertain significance Myofibrillar myopathy, ZASP-related 2018-03-05 criteria provided, single submitter clinical testing
Invitae RCV000661930 SCV000945451 uncertain significance Myofibrillar myopathy, ZASP-related 2020-04-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 145 of the LDB3 protein (p.Gly145Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs376489385, ExAC 0.02%). This variant has not been reported in the literature in individuals with LDB3-related disease. ClinVar contains an entry for this variant (Variation ID: 518946). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Klaassen Lab,Charite University Medicine Berlin RCV000853126 SCV000995838 uncertain significance Primary dilated cardiomyopathy 2019-07-03 criteria provided, single submitter research
Mayo Clinic Laboratories, Mayo Clinic RCV001509393 SCV001716077 uncertain significance not provided 2020-12-17 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.