Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001246592 | SCV001419955 | uncertain significance | Myofibrillar myopathy 4 | 2019-09-17 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with LDB3-related conditions. This variant is present in population databases (rs753237785, ExAC 0.05%). This sequence change replaces leucine with arginine at codon 717 of the LDB3 protein (p.Leu717Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. The LDB3 gene has multiple clinically relevant transcripts. The p.Leu717Arg variant occurs in alternate transcript NM_007078.2, which corresponds to c.*33568T>G in NM_001080116.1, the primary transcript listed in the Methods. |
Ambry Genetics | RCV002430045 | SCV002727187 | uncertain significance | Cardiovascular phenotype | 2022-06-09 | criteria provided, single submitter | clinical testing | The p.L717R variant (also known as c.2150T>G), located in coding exon 13 of the LDB3 gene, results from a T to G substitution at nucleotide position 2150. The leucine at codon 717 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. |