ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.690-4802C>A (rs755513516)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183549 SCV000236018 uncertain significance not provided 2014-09-30 criteria provided, single submitter clinical testing p.Pro124Thr (CCC>ACC): c.370 C>A in exon 5 of the LDB3 gene (NM_001080114.1). The P124T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The P124T variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P124T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in this transcript have not been reported in association with cardiomyopathy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Invitae RCV000536810 SCV000638674 uncertain significance Myofibrillar myopathy, ZASP-related 2020-10-06 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 124 of the LDB3 protein (p.Pro124Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs755513516, ExAC 0.003%) but has not been reported in the literature in individuals with a LDB3-related disease. ClinVar contains an entry for this variant (Variation ID: 201860). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000623559 SCV000740596 uncertain significance Primary familial dilated cardiomyopathy 2017-03-30 criteria provided, single submitter clinical testing

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