Description
The N406K likely pathogenic variant in the SCN5A gene has been reported previously in association with LQTS (Tester et al., 2005; Kato et al., 2014). N406K was reported as apparently de novo in a male with a QTc interval of 638 ms at 1 day old and 478 ms at 8 months old (Kato et al., 2014). The N406K variant is not observed in large population cohorts (Lek et al., 2016). The N406K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Furthermore, functional studies in Chinese hamster ovary cells demonstrated N406 alters the function of this sodium channel (Kato et al., 2014). Nevertheless, the N406K variant lacks observation in a significant number of affected individuals and segregation data, which would further clarify its pathogenicity.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |