Submissions for variant NM_007078.3(LDB3):c.1502C>T (p.Ala501Val)

gnomAD frequency: 0.00001  dbSNP: rs755362259

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000489670	SCV000577562	uncertain significance	not provided	2018-07-17	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the LDB3 gene. The A501V variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). However, the A501V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Fulgent Genetics, Fulgent Genetics	RCV000763675	SCV000894555	uncertain significance	Dilated cardiomyopathy 1C; Myofibrillar myopathy 4	2018-10-31	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852432	SCV000995116	uncertain significance	Cardiomyopathy	2018-05-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001320697	SCV001511492	uncertain significance	Myofibrillar myopathy 4	2023-10-29	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.*17223C>T in the primary transcript. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 501 of the LDB3 protein (p.Ala501Val). This variant is present in population databases (rs755362259, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of LDB3-related conditions (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000852432	SCV002043375	uncertain significance	Cardiomyopathy	2020-11-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000489670	SCV002585235	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing	LDB3: PM2, BP4
Ambry Genetics	RCV002395189	SCV002702381	uncertain significance	Cardiovascular phenotype	2023-10-21	criteria provided, single submitter	clinical testing	The p.A501V variant (also known as c.1502C>T), located in coding exon 9 of the LDB3 gene, results from a C to T substitution at nucleotide position 1502. The alanine at codon 501 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. 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.