ClinVar Miner

Submissions for variant NM_024334.2(TMEM43):c.418_420AAG[1] (p.Lys141del) (rs746639451)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000776206 SCV000911344 uncertain significance Cardiomyopathy 2018-10-27 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant causes a deletion of a single amino acid from the cytoplasmic domain of the TMEM43 protein. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 11/246172 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
GeneDx RCV000493985 SCV000582078 uncertain significance not provided 2017-05-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TMEM43 gene. The c.421_423delAAG variant has not been published as pathogenic or been reported as benign to our knowledge. The c.421_423delAAG variant results in an in-frame deletion of a lysine residue at position 141, denoted p.Lys141del. However, no other in-frame deletions or insertions, or pathogenic missense variants in nearby residues have been reported in Human Gene Mutation Database (Stenson et al., 2014). Nevertheless, c.421_423delAAG is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae RCV000822228 SCV000963020 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 5 2018-10-05 criteria provided, single submitter clinical testing This variant, c.421_423delAAG, results in the deletion of 1 amino acid(s) of the TMEM43 protein (p.Lys141del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs746639451, ExAC 0.009%). This variant has not been reported in the literature in individuals with TMEM43-related disease. ClinVar contains an entry for this variant (Variation ID: 429495). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.

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