Submissions for variant NM_007078.3(LDB3):c.1799G>A (p.Arg600Gln)

gnomAD frequency: 0.00001  dbSNP: rs747523570

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000767129	SCV000236010	uncertain significance	not provided	2012-07-31	criteria provided, single submitter	clinical testing	p.Arg600Gln (CGA>CAA):c.1799 G>A in exon 10 of the LDB3 gene (NM_007078.2). The Arg600Gln variant in the LDB3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg600Gln results in a semi-conservative amino acid substitution of a positively-charged Arginine with a neutral Glutamine at a position that is moderately conserved across species. In addition, no other mutations in surrounding residues have been reported in association with cardiomyopathy, indicating this region of the protein may be tolerant of change. The NHLBI ESP Exome Variant Server reports Arg600Gln was not observed in approximately 6000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Arg600Gln is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000183541	SCV000271912	uncertain significance	not specified	2015-08-12	criteria provided, single submitter	clinical testing	The p.Arg600Gln variant in LDB3 has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/66736 European chromosomes and 1/6614 Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summa ry, the clinical significance of the p.Arg600Gln variant is uncertain.
Invitae	RCV001241607	SCV001414635	uncertain significance	Myofibrillar myopathy 4	2019-10-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 600 of the LDB3 protein (p.Arg600Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. The LDB3 gene has multiple clinically relevant transcripts. The p.Arg600Gln variant occurs in alternate transcript NM_007078.2, which corresponds to c.*18712G>A in NM_001080116.1, the primary transcript listed in the Methods. This variant is present in population databases (rs747523570, ExAC 0.02%). This variant has not been reported in the literature in individuals with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 201854). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000767129	SCV001714353	uncertain significance	not provided	2020-01-22	criteria provided, single submitter	clinical testing