ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2103G>T (p.Leu701Phe)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003517590 SCV004248016 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 701 of the DSC2 protein (p.Leu701Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSC2 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.
All of Us Research Program, National Institutes of Health RCV004011349 SCV004834163 uncertain significance Familial isolated arrhythmogenic right ventricular dysplasia 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 701 of the DSC2 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 DSC2-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.

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