Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000038745 | SCV000062423 | uncertain significance | not specified | 2013-02-27 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The Cys636Tyr v ariant in LDB3 has not been reported in the literature but has been identified i n a child with DCM tested by our laboratory. This variant has also not been iden tified in large European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS), which increases the likelihood that it is pathogenic. However, we cannot exclude that it may be com mon in other populations. Computational analyses (biochemical amino acid propert ies, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Cys636Tyr va riant may impact the protein, though this information is not predictive enough t o determine pathogenicity. This data supports that the Cys636Tyr variant may be pathogenic but additional studies are needed to fully assess its clinical signif icance. |
| Invitae | RCV000814258 | SCV000954660 | uncertain significance | Myofibrillar myopathy 4 | 2018-10-26 | 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: "Not Available"; Align-GVGD: "Class C65"). This variant has been observed in an individual affected with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 45535). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 636 of the LDB3 protein (p.Cys636Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. The LDB3 gene has multiple clinically relevant transcripts. The p.Cys636Tyr variant occurs in alternate transcript NM_007078.2, which corresponds to position c.*19402G>A in NM_001080116.1, the primary transcript listed in the Methods. |