ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1907G>A (p.Cys636Tyr) (rs397517218)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized 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, ZASP-related 2018-10-29 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 45535). 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"). 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.

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