ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.896+6753C>T (rs121908335)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154745 SCV000204425 uncertain significance not specified 2014-07-10 criteria provided, single submitter clinical testing The Arg268Cys variant in LDB3 has been reported in 1 individual with clinical fe atures of myofibrillar myopathy (Selcen 2005). This variant has also been identi fied in 1/8284 of European American chromosomes by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS/; dbSNP rs121908335). Computational pred iction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogeni city. In summary, the clinical significance of the Arg268Cys variant is uncertai n.
Ambry Genetics RCV000620537 SCV000736804 uncertain significance Cardiovascular phenotype 2017-05-04 criteria provided, single submitter clinical testing The p.R268C variant (also known as c.802C>T), located in coding exon 8 of the LDB3 gene, results from a C to T substitution at nucleotide position 802. The arginine at codon 268 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in an individual with myofibrillar myopathy without cardiac involvement (Selcen D et al. Ann. Neurol., 2005 Feb;57:269-76). This alteration was also detected in an exome cohort, but clinical details were limited (Lee H et al. JAMA, 2014 Nov;312:1880-7). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000770982 SCV000897967 uncertain significance Dilated cardiomyopathy 1C 2018-06-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769280 SCV000900658 uncertain significance Cardiomyopathy 2017-07-04 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845475 SCV000987570 uncertain significance Primary familial dilated cardiomyopathy criteria provided, single submitter clinical testing
Invitae RCV000004994 SCV001229430 uncertain significance Myofibrillar myopathy, ZASP-related 2020-10-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 268 of the LDB3 protein (p.Arg268Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs121908335, ExAC 0.02%). This variant has been observed in individual(s) with clinical features of myofibrillar myopathy (PMID: 15668942, 25326637). ClinVar contains an entry for this variant (Variation ID: 4729). This variant has been reported to have conflicting or insufficient data to determine the effect on LDB3 protein function (PMID: 28349680). 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.
OMIM RCV000004994 SCV000025170 pathogenic Myofibrillar myopathy, ZASP-related 2005-02-01 no assertion criteria provided literature only

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