R1135H (p.Arg1135His) variant of SCN4A (Nav1.4)
R1135H (p.Arg1135His) in SCN4A (Nav1.4) is a missense change. Clinical records from ClinVar, EBI, and UniProt describe it as pathogenic in the context of Potassium-aggravated myotonia; Hypokalemic periodic paralysis, type 2; Congenita. The available variant effect predictions contribute to a CATVariant prioritization score of 0.90 / 1. The record also includes population frequency data, published literature, and structural context.
R1135H (p.Arg1135His) variant details
- p.Arg1135His
- rs527236150
- ClinGen CA345720
- ClinVar RCV000132737
- ClinVar RCV000254971
- Pathogenic
- Potassium-aggravated myotonia; Hypokalemic periodic paralysis, type 2; Congenita
- Missense
- Variant Prioritization Score for Impact Estimate 0.898
- REVEL 0.94
- AlphaMissense 1.00
- MetaLR 0.99
- MetaSVM 0.88
- CADD 29.20
- PolyPhen-2 1.00
- ClinVar: Pathogenic (Potassium-aggravated myotonia; Hypokalemic periodic paralysis, t)
- EBI: Pathogenic (in HOKPP2)
- UniProt: Pathogenic (in HOKPP2)
- Most common in the African/African-American population (allele frequency 3e-05)
- Structural context available
- Cited in: Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. (PMID 19118277)
- Cited in: NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery. (PMID 24549961)