Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000440929 | SCV000524025 | uncertain significance | not provided | 2017-01-16 | criteria provided, single submitter | clinical testing | The N556S variant of uncertain significance in the LDB3 gene has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, or in the Exome Aggregation Consortium, indicating it is not a common benign variant in these populations. However, the N556S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved, where S556 is the native residue in multiple species. In silico analysis predicts this variant likely does not alter the protein structure/function. |
Invitae | RCV000473699 | SCV000545679 | uncertain significance | Myofibrillar myopathy 4 | 2022-03-03 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs372583830, gnomAD 0.007%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 556 of the LDB3 protein (p.Asn556Ser). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17388A>G in the primary transcript. |
Ambry Genetics | RCV002402151 | SCV002709101 | uncertain significance | Cardiovascular phenotype | 2020-03-17 | criteria provided, single submitter | clinical testing | The p.N556S variant (also known as c.1667A>G), located in coding exon 9 of the LDB3 gene, results from an A to G substitution at nucleotide position 1667. The asparagine at codon 556 is replaced by serine, an amino acid with highly similar properties. This amino acid position is poorly 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. |