Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000462076 | SCV000545692 | uncertain significance | Myofibrillar myopathy 4 | 2016-08-11 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function and splicing. 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. While this variant is not present in population databases (ExAC no frequency), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a LDB3-related disease. This sequence change replaces threonine with serine at codon 443 of the LDB3 protein (p.Thr443Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. The LDB3 gene has multiple clinically relevant isoforms. The p.Thr443Ser variant occurs in alternate transcript NM_001171610.1, which corresponds to position c.*17034C>G in NM_001080116.1, the primary transcript listed in the Methods. |