Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Center of Genomic medicine, |
RCV000770982 | SCV000897967 | uncertain significance | Dilated cardiomyopathy 1C | 2018-06-01 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000769280 | SCV000900658 | uncertain significance | Cardiomyopathy | 2017-07-04 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000845475 | SCV000987570 | uncertain significance | Primary familial dilated cardiomyopathy | criteria provided, single submitter | clinical testing | ||
Invitae | RCV000004994 | SCV001229430 | uncertain significance | Myofibrillar myopathy 4 | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 268 of the LDB3 protein (p.Arg268Cys). This variant is present in population databases (rs121908335, gnomAD 0.01%). This missense change has been observed in individuals with clinical features of LDB3-related conditions (PMID: 15668942, 25326637; Invitae). ClinVar contains an entry for this variant (Variation ID: 4729). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on LDB3 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. |
Fulgent Genetics, |
RCV002490316 | SCV002796985 | uncertain significance | Dilated cardiomyopathy 1C; Myofibrillar myopathy 4 | 2021-09-18 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004994 | SCV000025170 | pathogenic | Myofibrillar myopathy 4 | 2005-02-01 | no assertion criteria provided | literature only |