Submissions for variant NM_007078.3(LDB3):c.676G>A (p.Gly226Arg)

gnomAD frequency: 0.00006  dbSNP: rs771099131

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001400520	SCV001602324	uncertain significance	Myofibrillar myopathy 4	2023-05-23	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 698920). This variant is present in population databases (rs771099131, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 226 of the LDB3 protein (p.Gly226Arg). 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+1633G>A in the primary transcript.
Ambry Genetics	RCV002363234	SCV002666515	uncertain significance	Cardiovascular phenotype	2022-02-08	criteria provided, single submitter	clinical testing	The p.G226R variant (also known as c.676G>A), located in coding exon 4 of the LDB3 gene, results from a G to A substitution at nucleotide position 676. The glycine at codon 226 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in a pediatric dilated cardiomyopathy (DCM) cohort (Herkert JC et al. Genet Med, 2018 11;20:1374-1386). 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	RCV000866542	SCV001740489	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000866542	SCV001926869	uncertain significance	not provided		no assertion criteria provided	clinical testing