Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000527115 | SCV000638682 | uncertain significance | Myofibrillar myopathy 4 | 2017-06-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with a LDB3-related disease. In summary, this variant has uncertain impact on LDB3 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 379 of the LDB3 protein (p.Ala379Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. The LDB3 gene has multiple clinically relevant isoforms. The p.Ala379Val variant occurs in alternate transcript NM_001171610.1, which corresponds to position c.*10566C>T in NM_001080116.1, the primary transcript listed in the Methods. |