Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000553647 | SCV000638664 | uncertain significance | Myofibrillar myopathy 4 | 2017-02-15 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with arginine at codon 417 of the LDB3 protein (p.Pro417Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. The LDB3 gene has multiple clinically relevant isoforms. The p.Pro417Arg variant occurs in alternate transcript NM_001171610.1, which corresponds to position c.*16956C>G in NM_001080116.1, the primary transcript listed in the Methods. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a LDB3-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |