ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.162G>C (p.Glu54Asp)

dbSNP: rs746126153
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181195 SCV001346295 uncertain significance Cardiomyopathy 2019-02-22 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is located in the TMEM43 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may 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 1/245070 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.
Invitae RCV003600403 SCV004370779 uncertain significance Arrhythmogenic right ventricular dysplasia 5 2023-05-15 criteria provided, single submitter clinical testing An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 921641). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. This variant is present in population databases (rs746126153, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 54 of the TMEM43 protein (p.Glu54Asp). This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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