Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000183533 | SCV000236000 | uncertain significance | not provided | 2012-07-24 | criteria provided, single submitter | clinical testing | p.Ala377Thr (GCA>ACA): c.1129 G>A in exon 8 of the LDB3 gene (NM_007078.2) The Ala377Thr variant in the LDB3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ala377Thr results in a non-conservative amino acid substitution of a non-polar Alanine with a neutral, polar Threonine at a position that is conserved across mammal species. The NHLBI ESP Exome Variant Server reports Ala377Thr 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. However, no mutations have been reported in nearby codons, indicating this region of the protein may tolerate change. In summary, with the clinical and molecular information available at this time, we cannot determine if Ala377Thr is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s). |
Invitae | RCV003765141 | SCV004622187 | uncertain significance | Myofibrillar myopathy 4 | 2022-11-08 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs794729061, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 377 of the LDB3 protein (p.Ala377Thr). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*10574G>A in the primary transcript. |