Submissions for variant NM_007078.3(LDB3):c.1211G>A (p.Arg404Gln)

gnomAD frequency: 0.00001  dbSNP: rs150868546

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000811214	SCV000951470	uncertain significance	Myofibrillar myopathy 4	2022-07-14	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 33500567). This variant is present in population databases (rs150868546, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 404 of the LDB3 protein (p.Arg404Gln). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*10656G>A in the primary transcript.
GeneDx	RCV001532131	SCV001991222	uncertain significance	not provided	2019-06-06	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Ambry Genetics	RCV002352412	SCV002653756	uncertain significance	Cardiovascular phenotype	2023-06-26	criteria provided, single submitter	clinical testing	The p.R404Q variant (also known as c.1211G>A), located in coding exon 8 of the LDB3 gene, results from a G to A substitution at nucleotide position 1211. The arginine at codon 404 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a left ventricular non-compaction (LVNC) cohort (Mazzarotto F et al. Genet Med, 2021 May;23:856-864). This amino acid position is 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.
Fulgent Genetics, Fulgent Genetics	RCV002487766	SCV002793531	uncertain significance	Dilated cardiomyopathy 1C; Myofibrillar myopathy 4	2021-11-02	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150352	SCV003837810	uncertain significance	Cardiomyopathy	2021-06-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001532131	SCV004563605	uncertain significance	not provided	2023-11-29	criteria provided, single submitter	clinical testing