Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617629 | SCV000737220 | uncertain significance | Cardiovascular phenotype | 2017-01-05 | criteria provided, single submitter | clinical testing | The p.R178W variant (also known as c.532C>T), located in coding exon 4 of the LDB3 gene, results from a C to T substitution at nucleotide position 532. The arginine at codon 178 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species, and tryptophan 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. |
| Invitae | RCV001448297 | SCV001651383 | uncertain significance | Myofibrillar myopathy 4 | 2023-05-23 | 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 is not likely to affect RNA splicing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 519144). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs730880128, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 178 of the LDB3 protein (p.Arg178Trp). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.321+1489C>T in the primary transcript. |
| Gene |
RCV001570098 | SCV001794313 | uncertain significance | not provided | 2020-12-18 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 519144; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this variant does not alter splicing |