ClinVar Miner

Submissions for variant NM_007078.3(LDB3):c.1253C>G (p.Pro418Arg) (rs141870580)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463144 SCV000545689 uncertain significance Myofibrillar myopathy, ZASP-related 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 418 of the LDB3 protein (c.1253C>G). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. The LDB3 gene has multiple clinically relevant transcripts. The c.1253C>G variant occurs in alternate transcript NM_007078.2, which corresponds to position c.*16974C>G in NM_001080116.1, the primary transcript listed in the Methods. This variant is present in population databases (rs141870580, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with LDB3-related disease. ClinVar contains an entry for this variant (Variation ID: 406810). 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: "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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000600447 SCV000710911 uncertain significance not specified 2016-06-16 criteria provided, single submitter clinical testing The p.Pro418Arg variant in LDB3 has not been previously reported in individuals with cardiomyopathy, but has been identified in 14/65594 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s141870580). Computational prediction tools and conservation analysis suggest th at the p.Pro418Arg variant may impact the protein, though this information is no t predictive enough to determine pathogenicity. In summary, the clinical signifi cance of the p.Pro418Arg variant is uncertain.
Ambry Genetics RCV000621788 SCV000737217 uncertain significance Cardiovascular phenotype 2017-01-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000622484 SCV000740598 uncertain significance Familial dilated cardiomyopathy 2017-05-23 criteria provided, single submitter clinical testing

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