Submissions for variant NM_007078.3(LDB3):c.1336A>G (p.Thr446Ala)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002300925	SCV002588199	uncertain significance	not provided	2022-04-28	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Note that the p.(T446A) variant is present in an alternate transcript of the LDB3 gene (NM_007078.2), and is not present in the coding portion of the primary transcript (NM_001080116.1).
Ambry Genetics	RCV002382512	SCV002692636	uncertain significance	Cardiovascular phenotype	2021-06-22	criteria provided, single submitter	clinical testing	The p.T446A variant (also known as c.1336A>G), located in coding exon 9 of the LDB3 gene, results from an A to G substitution at nucleotide position 1336. The threonine at codon 446 is replaced by alanine, 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.
Invitae	RCV003611578	SCV004519121	uncertain significance	Myofibrillar myopathy 4	2022-11-14	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 variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 446 of the LDB3 protein (p.Thr446Ala). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*17057A>G in the primary transcript.