ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.889T>A (p.Phe297Ile)

dbSNP: rs990243563
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001887284 SCV002159067 uncertain significance Arrhythmogenic right ventricular dysplasia 5 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 297 of the TMEM43 protein (p.Phe297Ile). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 1395869). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMEM43 protein function. 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.
Ambry Genetics RCV002370467 SCV002685543 uncertain significance Cardiovascular phenotype 2021-10-01 criteria provided, single submitter clinical testing The p.F297I variant (also known as c.889T>A), located in coding exon 11 of the TMEM43 gene, results from a T to A substitution at nucleotide position 889. The phenylalanine at codon 297 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002482748 SCV002787108 uncertain significance Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominant; Auditory neuropathy, autosomal dominant 3 2021-08-18 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003533048 SCV004359879 uncertain significance Cardiomyopathy 2022-11-07 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with isoleucine at codon 297 of the TMEM43 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TMEM43-related disorders in the literature. This variant has been identified in 1/251426 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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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