Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000805577 | SCV000945537 | uncertain significance | Myofibrillar myopathy 4 | 2021-08-16 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 555 of the LDB3 protein (p.Asn555Ser). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17385 in the primary transcript. |
| Ambry Genetics | RCV003380731 | SCV004096714 | uncertain significance | Cardiovascular phenotype | 2023-07-17 | criteria provided, single submitter | clinical testing | The p.N555S variant (also known as c.1664A>G), located in coding exon 9 of the LDB3 gene, results from an A to G substitution at nucleotide position 1664. The asparagine at codon 555 is replaced by serine, an amino acid with highly similar properties. This variant co-occurred with a TTN A-band truncating variant in an individual reported to have dilated cardiomyopathy (Horvat C et al. Genet Med, 2019 Jan;21:133-143). This amino acid position is highly 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. |