ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.458C>T (p.Pro153Leu)

gnomAD frequency: 0.00001  dbSNP: rs1298498462
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001229753 SCV001402208 uncertain significance Brugada syndrome 2022-02-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 153 of the SCN5A protein (p.Pro153Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 956871). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224533 SCV003920453 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2022-07-25 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest rpeorted MAF: 0.007% [1/15288]; https://gnomad.broadinstitute.org/variant/3-38622424-G-A?dataset=gnomad_r3), and in ClinVar (Variation ID:956871). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003486971 SCV004239674 uncertain significance Cardiomyopathy 2022-12-29 criteria provided, single submitter clinical testing

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