ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.356C>T (p.Ala119Val) (rs397517223)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767123 SCV000235989 uncertain significance not provided 2015-08-04 criteria provided, single submitter clinical testing p.Ala119Val (GCA>GTA): c.356 C>T in exon 4 of the LDB3 gene (NM_007078.2). The A119V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A119V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, another missense mutation in a nearby residue (D117N) has been reported in association with DCM, supporting the functional importance of this region of the protein. However, the A119V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. 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 RCV000807856 SCV000947932 uncertain significance Myofibrillar myopathy, ZASP-related 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 119 of the LDB3 protein (p.Ala119Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. The LDB3 gene has multiple clinically relevant transcripts. The p.Ala119Val variant occurs in alternate transcript NM_007078.2, which corresponds to position c.321+1313C>T (Intronic) in NM_001080116.1, the primary transcript listed in the Methods. This variant is present in population databases (rs397517223, ExAC 0.002%). This variant has not been reported in the literature in individuals with LDB3-related disease. ClinVar contains an entry for this variant (Variation ID: 45545). 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: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038757 SCV000062435 uncertain significance not specified 2014-05-23 no assertion criteria provided clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

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