Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697140 | SCV000825735 | uncertain significance | Myofibrillar myopathy 4 | 2018-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 378 of the LDB3 protein (p.Pro378Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. The LDB3 gene has multiple clinically relevant transcripts. The p.Pro378Ser variant occurs in alternate transcript NM_007078.2, which corresponds to position c.*10577C>T in NM_001080116.1, the primary transcript listed in the Methods. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LDB3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, 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. 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. |
Ambry Genetics | RCV002442482 | SCV002612365 | uncertain significance | Cardiovascular phenotype | 2022-10-20 | criteria provided, single submitter | clinical testing | The p.P378S variant (also known as c.1132C>T), located in coding exon 8 of the LDB3 gene, results from a C to T substitution at nucleotide position 1132. The proline at codon 378 is replaced by serine, an amino acid with similar properties. 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. |