ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1798C>T (p.Arg600Ter) (rs727503132)

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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 RCV000150930 SCV000198574 uncertain significance not specified 2014-04-16 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Arg600X var iant in LDB3 has not been reported in individuals with cardiomyopathy or in larg e population studies. This nonsense variant leads to a premature termination cod on at position 600, which is predicted to lead to a truncated or absent protein (loss-of-function). Studies of mouse models support that absence of LDB3 in the heart leads to DCM (Zheng 2009); however, this has not been well studied in huma ns. Our laboratory has detected homozygous/compound heterozygous loss-of-functio n variants in LDB3 in 2 neonates with DCM +/- LVNC and 1 individual with VT and SCA carried heterozygous loss of function variant. These data suggest that loss- of-function variants in LDB3 are pathogenic in the homozygous/compound heterozyg ous state but additional studies are needed to fully establish their clinical si gnificance
Invitae RCV000799668 SCV000939342 uncertain significance Myofibrillar myopathy, ZASP-related 2018-10-08 criteria provided, single submitter clinical testing This sequence change results in a premature translation stop signal in the LDB3 protein (p.Arg600*). It is expected to result in an absent or disrupted protein product. The LDB3 gene has multiple clinically relevant transcripts. The p.Arg600* variant occurs in alternate transcript NM_007078.2, which corresponds to position c.*18711C>T in NM_001080116.1, the primary transcript listed in the Methods. This variant is present in population databases (rs727503132, ExAC 0.05%). This variant has not been reported in the literature in individuals with LDB3-related disease. ClinVar contains an entry for this variant (Variation ID: 163853). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LDB3 cause disease. 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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