Submissions for variant NM_024334.3(TMEM43):c.458C>T (p.Ser153Leu)

dbSNP: rs1369869806

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001190374	SCV001357837	uncertain significance	Cardiomyopathy	2023-03-09	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 153 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). 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 not been identified 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.
Invitae	RCV001863019	SCV002159993	uncertain significance	Arrhythmogenic right ventricular dysplasia 5	2023-05-01	criteria provided, single submitter	clinical testing	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. 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 expected to disrupt TMEM43 protein function. ClinVar contains an entry for this variant (Variation ID: 927252). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 153 of the TMEM43 protein (p.Ser153Leu).
Ambry Genetics	RCV002339478	SCV002637052	uncertain significance	Cardiovascular phenotype	2022-07-10	criteria provided, single submitter	clinical testing	The p.S153L variant (also known as c.458C>T), located in coding exon 6 of the TMEM43 gene, results from a C to T substitution at nucleotide position 458. The serine at codon 153 is replaced by leucine, 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	RCV002491573	SCV002787626	uncertain significance	Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominant; Auditory neuropathy, autosomal dominant 3	2021-10-15	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003142113	SCV003827653	uncertain significance	not provided	2021-06-10	criteria provided, single submitter	clinical testing