Submissions for variant NM_007078.3(LDB3):c.1313C>A (p.Thr438Asn)

gnomAD frequency: 0.00001  dbSNP: rs767914340

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001361255	SCV001557224	uncertain significance	Myofibrillar myopathy 4	2023-06-24	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 variant has not been reported in the literature in individuals affected with LDB3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 438 of the LDB3 protein (p.Thr438Asn). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17034C>A in the primary transcript.
Ambry Genetics	RCV002384510	SCV002692042	uncertain significance	Cardiovascular phenotype	2023-09-13	criteria provided, single submitter	clinical testing	The p.T438N variant (also known as c.1313C>A), located in coding exon 9 of the LDB3 gene, results from a C to A substitution at nucleotide position 1313. The threonine at codon 438 is replaced by asparagine, an amino acid with similar properties. This variant has been detected in an individual reported to have alcohol-induced cardiomyopathy (Ware JS et al. J Am Coll Cardiol. 2018 May;71(20):2293-2302). 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001574025	SCV001800716	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001574025	SCV001969122	uncertain significance	not provided		no assertion criteria provided	clinical testing