ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.447dup (p.Glu150Ter)

gnomAD frequency: 0.00004  dbSNP: rs1423539317
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001185518 SCV001351754 uncertain significance Cardiomyopathy 2023-07-20 criteria provided, single submitter clinical testing This variant inserts 1 nucleotide in exon 6 of the TMEM43 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. 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 4/251466 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical significance of loss-of-function truncation variants in the TMEM43 gene is not clearly established. Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001203047 SCV001374193 uncertain significance Arrhythmogenic right ventricular dysplasia 5 2024-10-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu150*) in the TMEM43 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TMEM43 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. ClinVar contains an entry for this variant (Variation ID: 809429). 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.
Fulgent Genetics, Fulgent Genetics RCV002479181 SCV002782807 uncertain significance Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominant; Auditory neuropathy, autosomal dominant 3 2021-10-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV003307794 SCV004000720 uncertain significance Cardiovascular phenotype 2023-05-04 criteria provided, single submitter clinical testing The c.447dupT variant, located in coding exon 6 of the TMEM43 gene, results from a duplication of T at nucleotide position 447, causing a translational frameshift with a predicted alternate stop codon (p.E150*). This variant has been detected through exome sequencing in a cohort not selected for the presence of cardiovascular disease; however, details were limited (Van Hout CV et al. Nature, 2020 10;586:749-756). This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of TMEM43 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV001203047 SCV004841508 uncertain significance Arrhythmogenic right ventricular dysplasia 5 2024-07-29 criteria provided, single submitter clinical testing This variant inserts 1 nucleotide in exon 6 of the TMEM43 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. 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 4/251466 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical significance of loss-of-function truncation variants in the TMEM43 gene is not clearly established. Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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