Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001242696 | SCV001415799 | uncertain significance | Myofibrillar myopathy 4 | 2022-04-08 | criteria provided, single submitter | clinical testing | The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3 and corresponds to NM_001080116.1:c.*7156_*7157del in the primary transcript. This sequence change affects an acceptor splice site in intron 7 of the LDB3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LDB3 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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 | RCV002447204 | SCV002682115 | uncertain significance | Cardiovascular phenotype | 2019-12-02 | criteria provided, single submitter | clinical testing | The c.897-1_897delGC variant results from the deletion of 2 nucelotides at the c.897-1 and c.897 positions in the LDB3 gene. These nucleotide positions are well conserved through mammals. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native acceptor splice site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of LDB3 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002484335 | SCV002787041 | uncertain significance | Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 | 2021-08-02 | criteria provided, single submitter | clinical testing |