Submissions for variant NM_024334.3(TMEM43):c.31C>G (p.Arg11Gly)

dbSNP: rs201085402

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001192071	SCV001360016	uncertain significance	Cardiomyopathy	2020-03-02	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glycine at codon 11 of the TMEM43 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/251404 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.
GeneDx	RCV002307696	SCV002601555	uncertain significance	not provided	2022-11-10	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics	RCV002447031	SCV002612360	uncertain significance	Cardiovascular phenotype	2022-01-19	criteria provided, single submitter	clinical testing	The p.R11G variant (also known as c.31C>G), located in coding exon 2 of the TMEM43 gene, results from a C to G substitution at nucleotide position 31. The arginine at codon 11 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002504216	SCV002812760	uncertain significance	Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominant; Auditory neuropathy, autosomal dominant 3	2021-08-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV005094020	SCV005831396	uncertain significance	Arrhythmogenic right ventricular dysplasia 5	2024-07-03	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 11 of the TMEM43 protein (p.Arg11Gly). This variant is present in population databases (rs201085402, 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: 928295). 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 tolerated. 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.