Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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. |