ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.54G>T (p.Gln18His) (rs149348427)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183544 SCV000236013 uncertain significance not provided 2018-03-05 criteria provided, single submitter clinical testing The Q18H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q18H variant was not observed with any significant frequency in approximately 6500 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 Q18H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with DCM (Stenson et al., 2014), indicating this region of the gene is not known to harbor disease-causing variants. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Fulgent Genetics,Fulgent Genetics RCV000763672 SCV000894552 uncertain significance Dilated cardiomyopathy 1C; Myofibrillar myopathy, ZASP-related 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000817342 SCV000957896 uncertain significance Myofibrillar myopathy, ZASP-related 2018-10-26 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 18 of the LDB3 protein (p.Gln18His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs149348427, ExAC 0.009%). This variant has been observed in an individual who suffered a sudden unexplained death (PMID: 27005929). ClinVar contains an entry for this variant (Variation ID: 201856). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000845500 SCV000987602 uncertain significance Primary familial dilated cardiomyopathy criteria provided, single submitter clinical testing

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