ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs727503132
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham 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 pathogenic Myofibrillar myopathy 4 2023-05-08 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.*18711C>T in the primary transcript. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs727503132, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg600*) in the LDB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDB3 are known to be pathogenic (PMID: 36253531).
Ambry Genetics RCV002408668 SCV002717263 uncertain significance Cardiovascular phenotype 2022-01-25 criteria provided, single submitter clinical testing The p.R600* variant (also known as c.1798C>T), located in coding exon 10 of the LDB3 gene, results from a C to T substitution at nucleotide position 1798. This changes the amino acid from an arginine to a stop codon within coding exon 10. This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of LDB3 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002492556 SCV002780371 uncertain significance Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 2021-11-17 criteria provided, single submitter clinical testing

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