ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.4394T>C (p.Ile1465Thr)

gnomAD frequency: 0.00001  dbSNP: rs794728882
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183073 SCV000235482 uncertain significance not provided 2017-11-15 criteria provided, single submitter clinical testing The Ile1466Thr variant in the SCN5A gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ile1466Thr results in a non-conservative amino acid substitution of a neutral non-polar, Isoleucine residue, for a neutral polar Threonine residue at a position that is conserved across species. In silico analysis predicts Ile1466Thr is probably damaging to the protein structure/function. Mutations in nearby residues (Asn1463Tyr, Val1468Phe) have been reported in association with Brugada syndrome. The NHLBI ESP Exome Variant Server reports Ile1466Thr was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Ile1466Thr is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s).
Color Diagnostics, LLC DBA Color Health RCV001842922 SCV001343445 uncertain significance Cardiac arrhythmia 2023-06-01 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 1466 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 SCN5A-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.
All of Us Research Program, National Institutes of Health RCV001842922 SCV004830854 uncertain significance Cardiac arrhythmia 2023-09-17 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 1466 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 SCN5A-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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