Submissions for variant NM_007078.3(LDB3):c.610G>A (p.Ala204Thr)

gnomAD frequency: 0.00005  dbSNP: rs774976112

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770147	SCV000901573	uncertain significance	Cardiomyopathy	2017-10-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000869617	SCV001011057	uncertain significance	Myofibrillar myopathy 4	2024-11-21	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.321+1567G>A in the primary transcript. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 204 of the LDB3 protein (p.Ala204Thr). This variant is present in population databases (rs774976112, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32880476). ClinVar contains an entry for this variant (Variation ID: 626705). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx	RCV001529014	SCV001831974	uncertain significance	not provided	2019-03-21	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32880476)
Ambry Genetics	RCV002352279	SCV002660014	uncertain significance	Cardiovascular phenotype	2024-09-04	criteria provided, single submitter	clinical testing	The p.A204T variant (also known as c.610G>A), located in coding exon 4 of the LDB3 gene, results from a G to A substitution at nucleotide position 610. The alanine at codon 204 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort and a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited in both cases (Micheu MM et al. Diagnostics (Basel), 2020 Dec;10:[ePub ahead of print]; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 10;13:476-487). This amino acid position is 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529014	SCV001741736	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529014	SCV001953767	uncertain significance	not provided		no assertion criteria provided	clinical testing