Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002354148 | SCV002655818 | uncertain significance | Cardiovascular phenotype | 2019-05-16 | criteria provided, single submitter | clinical testing | The p.T206I variant (also known as c.617C>T), located in coding exon 4 of the LDB3 gene, results from a C to T substitution at nucleotide position 617. The threonine at codon 206 is replaced by isoleucine, an amino acid with similar properties. In one study, this variant (also referred to as p.T213I, c.638C>T) was detected in a pediatric proband reported to have dilated cardiomyopathy (DCM), noncompaction, and conduction disease that improved on follow up to mild DCM. The parents were reportedly unaffected and did not have the variant. It is unclear if other genes associated with cardiomyopathy were analyzed in the proband (Vatta M et al. J. Am. Coll. Cardiol., 2003 Dec;42:2014-27). Functional studies suggest this variant may have some impact on protein function, but the clinical relevance is unclear (Arimura T et al. Cardiovasc. Res., 2009 Jul;83:80-8; Lin C et al. J. Biol. Chem., 2013 Oct;288:29403-13). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV002512790 | SCV003264904 | uncertain significance | Myofibrillar myopathy 4 | 2023-08-30 | criteria provided, single submitter | clinical testing | The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.321+1574C>T in the primary transcript. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 206 of the LDB3 protein (p.Thr206Ile). This variant is present in population databases (rs121908337, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of LDB3-related conditions and/or dilated cardiomyopathy (PMID: 14662268; Invitae). This variant is also known as T213I. ClinVar contains an entry for this variant (Variation ID: 4732). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects LDB3 function (PMID: 19377068). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
| OMIM | RCV000004997 | SCV000025173 | pathogenic | Dilated cardiomyopathy 1C | 2003-12-03 | no assertion criteria provided | literature only |