See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

To date, most SCN8A pathogenic variants, including missense variants, splice site variants, and small deletions/duplications, are detectable by sequencing [Rauch et al 2012, Veeramah et al 2012, Allen et al 2013, Carvill et al 2013, de Kovel et al 2014, Estacion et al 2014, Ohba et al 2014, Vaher et al 2014, Blanchard et al 2015, Dyment et al 2015, Fitzgerald et al 2015, Fung et al 2015, Kong et al 2015a, Larsen et al 2015, Mercimek-Mahmutoglu et al 2015, Olson et al 2015, Singh et al 2015, Takahashi et al 2015, Wagnon et al 2015a, Anand et al 2016, Boerma et al 2016, Gardella et al 2016, Malcolmson et al 2016, Butler et al 2017, Han et al 2017, Jain 2017, Wagnon et al 2017, Wang et al 2017, Bagnasco et al 2018, Epilepsy Genetics Initiative 2018, Gardella et al 2018, Pons et al 2018, Wagnon et al 2018, Xiao et al 2018, Denis et al 2019, Epifanio et al 2019, Johannesen et al 2019, Kim et al 2019, Liao et al 2019, Lin et al 2019, Trivisano et al 2019, Wengert et al 2019, Zaman et al 2019, Canafoglia et al 2020, Fatema et al 2020, Ranza et al 2020, Schreiber et al 2020, Alagia et al 2021, Fan et al 2021, Negishi et al 2021, Solazzi et al 2021, Stringer et al 2021, Hu et al 2022, Johannesen et al 2022, Keshri et al 2022, Medlin et al 2022, Peng et al 2022]. Data is also derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020].

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Small deletions and/or duplications in SCN8A have been rarely reported [Berghuis et al 2015, Larsen et al 2015, Wong et al 2021, Johannesen et al 2022].

To date, no large chromosomal deletions/duplications have been reported in individuals with SCN8A-related epilepsy and/or neurodevelopmental disorders.