ClinVar Miner

Submissions for variant NM_024334.3(TMEM43):c.1013C>T (p.Pro338Leu)

dbSNP: rs17856369
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001192158 SCV001360152 uncertain significance Cardiomyopathy 2023-06-01 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 338 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 1/250486 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.
Invitae RCV001863049 SCV002315754 uncertain significance Arrhythmogenic right ventricular dysplasia 5 2022-10-13 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 928339). This variant has not been reported in the literature in individuals affected with TMEM43-related conditions. This variant is present in population databases (rs17856369, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 338 of the TMEM43 protein (p.Pro338Leu). 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. 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.
AiLife Diagnostics, AiLife Diagnostics RCV002224018 SCV002502585 uncertain significance not provided 2021-10-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002375116 SCV002624017 uncertain significance Cardiovascular phenotype 2023-01-24 criteria provided, single submitter clinical testing The p.P338L variant (also known as c.1013C>T), located in coding exon 12 of the TMEM43 gene, results from a C to T substitution at nucleotide position 1013. The proline at codon 338 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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