Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001892926 | SCV002162400 | uncertain significance | Myofibrillar myopathy 4 | 2021-02-22 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with LDB3-related conditions. This variant is present in population databases (rs146414300, ExAC 0.01%). This sequence change replaces alanine with threonine at codon 217 of the LDB3 protein (p.Ala217Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. |
| Ambry Genetics | RCV002422977 | SCV002677265 | uncertain significance | Cardiovascular phenotype | 2019-11-13 | criteria provided, single submitter | clinical testing | The p.A264T variant (also known as c.790G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide position 790. The alanine at codon 264 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other 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. |
| ARUP Laboratories, |
RCV003120737 | SCV003800114 | uncertain significance | not provided | 2022-06-30 | criteria provided, single submitter | clinical testing | The LDB3 c.649G>A, p.Ala217Thr variant (rs146414300), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 217 is highly conserved, but computational analyses predict that this variant is neutral (REVEL: 0.144). However, given the lack of clinical and functional data, the significance of the p.Ala217Thr variant is uncertain at this time. |