ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1225C>A (p.Gln409Lys) (rs139104492)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000344660 SCV000329396 uncertain significance not provided 2020-02-26 criteria provided, single submitter clinical testing Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#264565; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25617006)
Invitae RCV000539708 SCV000638683 uncertain significance Myofibrillar myopathy, ZASP-related 2020-01-21 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 409 of the LDB3 protein (p.Gln409Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between the two amino acids. The LDB3 gene has multiple clinically relevant isoforms. The p.Gln409Lys variant occurs in alternate transcript NM_007078.2, which corresponds to NM_001080116.1:c.*10670C>A in the primary transcript. This variant is present in population databases (rs139104492, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with inclusion body myositis (PMID: 25617006). This variant is also known as c.1240C>A (p.Q414K) in the literature. Clinvar contains an entry for this variant (Variation ID: 279835). 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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV001256802 SCV001433255 uncertain significance Dilated cardiomyopathy 1A 2020-03-27 criteria provided, single submitter clinical testing

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