Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000767013 | SCV000491832 | uncertain significance | not provided | 2017-06-02 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the LDB3 gene. The K184E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K184E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Though also not observed in these aforementioned populations by the Exome Aggregation Consortium (ExAc), ExAc did observe K184E in 10/11522 (0.09%) alleles from individuals of Latino background. The K184E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. |
Invitae | RCV001079727 | SCV000638694 | likely benign | Myofibrillar myopathy 4 | 2023-08-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000619242 | SCV000737247 | uncertain significance | Cardiovascular phenotype | 2017-02-17 | criteria provided, single submitter | clinical testing | The p.K184E variant (also known as c.550A>G), located in coding exon 4 of the LDB3 gene, results from an A to G substitution at nucleotide position 550. The lysine at codon 184 is replaced by glutamic acid, an amino acid with some similar properties. 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 variant remains unclear. |
New York Genome Center | RCV001836757 | SCV002097661 | uncertain significance | Dilated cardiomyopathy 1C | 2020-07-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000223723 | SCV004122629 | likely benign | not specified | 2023-10-09 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003967607 | SCV004782143 | likely benign | LDB3-related disorder | 2023-11-16 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000223723 | SCV000280178 | uncertain significance | not specified | 2015-02-17 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. LDB3 p.Lys184Glu Based on the data reviewed below we consider this variant of unknown significance, probably benign. The p.K184E variant (also known as c.550A>G) is located in coding exon 4 of the LDB3 gene. The lysine at codon 184 is replaced by glutamic acid, an amino acid with some similar properties. A journal search did not elucidate any previous reports of this variant in association with disease. In silico analysis with PolyPhen-2 predicts the variant to be benign. The 184 at codon is not well conserved across vertebrate species. In total the variant has not been seen in ~6,500 laboratory controls, published controls and individuals from publicly available population datasets. There is no variation at codon 184 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 7/27/13). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 7/25/13). |