SCN5A Variant Browser

Here we have a comprehensive list of variants in SCN5A found in individuals affected and unaffected with the two diseases most commonly associated with variants in SCN5A: Brugada Syndrome (BrS1; OMIM: 601144) and long QT type 3 (LQT3; OMIM: 603830). Coding variants are referenced to isoform Q14524-1 (ENST00000333535.9) to match convention. 'Total Carriers' is the number of heterozygotes diagnosed with LQT3, BrS1, Unaffected with disease, and found in the genome aggregation database (gnomAD). 'Other' is the number of heterozygoes diagnosed with a cardiac disease which is not LQT3 or BrS1. Click the variant link for more details. Functional classification of variants was done according to the following criteria for sodium channel peak tail current, stead state voltage of activation, and/or late/persistent current: Loss-of-function (LOF) < 10% peak, partial LOF <50% peak, mild LOF 50-75% peak, normal 75-125% peak, Gain-of-function (GOF) > 125% peak current or >300% late current, partial LOF >10 mV rightward shift in V0.5 activation. Structurally, a "Non_Hotspot" variant was surrounded by variants with <10% BrS1 penetrance on average, a "Mild_Hotspot" variant was surrounded by variants with between 10% and 40% BrS1 penetrance, on average, a "Hotspot" variant was surrounded by variants with greater than 40% BrS1 penetrance, on average.

Histogram of SCN5A Variant Carriers with BrS1

Below is histogram of the number of heterozygous carriers of SCN5A variants observed in individuals diagnosed with BrS1 displayed in the table above. The y-axis is the number of unique variants and the x-axis shows the number of heterozygous carriers.

Histogram of SCN5A Variant Carriers with LQT3

Below is histogram of the number of heterozygous carriers of SCN5A variants observed in individuals diagnosed with LQT3 displayed in the table above. The y-axis is the number of unique variants and the x-axis shows the number of heterozygous carriers.

Histogram of Putative Unaffected Heterozygous SCN5A Variant Carriers

Below is a histogram of the number of heterozygous carriers of SCN5A variants observed in unaffected individuals and in gnomAD (given the rarity of the BrS1 and LQT3 phenotypes in the general public, we assume these individuals are also likely unaffected) displayed in the table above. The y-axis is the number of unique variants (log scale) and the x-axis shows the number of heterozygous carriers (truncated at 300 to aid visualization).

Histogram of BrS1 Penetrance Estimates for SCN5A Variants

Below is a histogram of the estimates of BrS1 penetrance for all variants displayed in the table above. The range is from 0% (impossible) to 100% (certain).

Histogram of LQT3 Penetrance Estimates for SCN5A Variants

Below is a histogram of the estimates of LQT3 penetrance for all variants displayed in the table above. The range is from 0% (impossible) to 100% (certain).