Submissions for variant NM_007078.3(LDB3):c.608C>T (p.Ser203Leu)

gnomAD frequency: 0.00002  dbSNP: rs201538257

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001246528	SCV001419887	uncertain significance	Myofibrillar myopathy 4	2023-10-20	criteria provided, single submitter	clinical testing	The LDB3 gene has multiple clinically relevant transcripts. The p.Ser203Leu variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.321+1565C>T in the primary transcript. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 203 of the LDB3 protein (p.Ser203Leu). This variant is present in population databases (rs201538257, gnomAD 0.005%). This missense change has been observed in individual(s) with clinical features of LDB3-related conditions (PMID: 30471092, 32880476, 34088380). ClinVar contains an entry for this variant (Variation ID: 970872). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529613	SCV001743353	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529613	SCV001957671	uncertain significance	not provided		no assertion criteria provided	clinical testing