Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000469085 | SCV000545681 | uncertain significance | Myofibrillar myopathy 4 | 2023-12-28 | 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.*17166C>T in the primary transcript. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 482 of the LDB3 protein (p.Ala482Val). This variant is present in population databases (rs774313535, gnomAD 0.02%). 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: 406802). 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Gene |
RCV001545919 | SCV001765340 | likely benign | not provided | 2021-04-06 | criteria provided, single submitter | clinical testing | Not reported in association with a cardiac phenotype to our knowledge; In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID 406802; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 25344691) |
| Ambry Genetics | RCV002393101 | SCV002701529 | likely benign | Cardiovascular phenotype | 2024-03-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |