ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.530C>T (p.Ala177Val) (rs397517224)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155606 SCV000205314 uncertain significance not specified 2013-10-15 criteria provided, single submitter clinical testing The Ala177Val variant in LDB3 has been identified by our laboratory in 1 Caucasi an individual with DCM and data from large population studies is insufficient to assess its frequency. Computational analyses (biochemical amino acid properties , conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support fo r or against an impact to the protein. Additional information is needed to fully assess the clinical significance of the Ala177Val variant.
Invitae RCV000701572 SCV000830379 uncertain significance Myofibrillar myopathy, ZASP-related 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 177 of the LDB3 protein (p.Ala177Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. The LDB3 gene has multiple clinically relevant transcripts. The p.Ala177Val variant occurs in alternate transcript NM_007078.2, which corresponds to position c.321+1487C>T in NM_001080116.1, the primary transcript listed in the Methods. This variant is present in population databases (rs397517224, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with left ventricular noncompaction (PMID: 28798025). ClinVar contains an entry for this variant (Variation ID: 178834). 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: "Deleterious"; PolyPhen-2: "Benign"; 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770143 SCV000901569 uncertain significance Cardiomyopathy 2016-10-05 criteria provided, single submitter clinical testing

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