Submissions for variant NM_007078.3(LDB3):c.944C>T (p.Pro315Leu)

gnomAD frequency: 0.00004  dbSNP: rs371649487

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001307092	SCV001496485	uncertain significance	Myofibrillar myopathy 4	2023-12-06	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.*7204C>T in the primary transcript. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 315 of the LDB3 protein (p.Pro315Leu). This variant is present in population databases (rs371649487, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. 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.
Ambry Genetics	RCV002447312	SCV002683015	uncertain significance	Cardiovascular phenotype	2021-11-29	criteria provided, single submitter	clinical testing	The p.P315L variant (also known as c.944C>T), located in coding exon 7 of the LDB3 gene, results from a C to T substitution at nucleotide position 944. The proline at codon 315 is replaced by leucine, an amino acid with similar properties. This variant was detected in a cardiomyopathy/arrhythmia genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). 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 alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV001529572	SCV004127010	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	LDB3: BP4
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529572	SCV001743225	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001529572	SCV001922503	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529572	SCV001930612	uncertain significance	not provided		no assertion criteria provided	clinical testing