Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000806735 | SCV000946750 | uncertain significance | Myofibrillar myopathy 4 | 2019-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with arginine at codon 629 of the LDB3 protein (p.Trp629Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. The LDB3 gene has multiple clinically relevant transcripts. The p.Trp629Arg variant occurs in alternate transcript NM_007078.2, which corresponds to position c.*19380T>C in NM_001080116.1, the primary transcript listed in the Methods. This variant is present in population databases (rs773554501, ExAC 0.009%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65). 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 | RCV003307487 | SCV003995618 | uncertain significance | Cardiovascular phenotype | 2023-04-03 | criteria provided, single submitter | clinical testing | The p.W629R variant (also known as c.1885T>C), located in coding exon 11 of the LDB3 gene, results from a T to C substitution at nucleotide position 1885. The tryptophan at codon 629 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |