Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000183537 | SCV000236005 | uncertain significance | not provided | 2017-04-11 | criteria provided, single submitter | clinical testing | p.Pro523Ala (CCA>GCA): c.1567 C>G in exon 9 of the LDB3 gene (NM_007078.2). The Pro523Ala variant in the LDB3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Pro523Ala results in a semi-conservative amino acid substitution of sterically constrained Proline with a non-polar Alanine at a position that is conserved across species. In silico analysis predicts Pro523Ala is possibly damaging to the protein structure/function. Additionally, the NHLBI ESP Exome Variant Server reports Pro523Ala was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby codons have been reported in association with cardiomyopathy. With the clinical and molecular information available at this time, we cannot definitively determine if Pro523Ala is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s). |
| Ambry Genetics | RCV002399673 | SCV002708766 | uncertain significance | Cardiovascular phenotype | 2022-06-06 | criteria provided, single submitter | clinical testing | The p.P523A variant (also known as c.1567C>G), located in coding exon 9 of the LDB3 gene, results from a C to G substitution at nucleotide position 1567. The proline at codon 523 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| Fulgent Genetics, |
RCV002485226 | SCV002792128 | uncertain significance | Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 | 2021-07-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003765142 | SCV004651653 | uncertain significance | Myofibrillar myopathy 4 | 2023-08-31 | criteria provided, single submitter | clinical testing | The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17291G>A in the primary transcript. This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 523 of the LDB3 protein (p.Pro523Ala). This variant is present in population databases (rs794729062, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 201850). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |