ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.134G>A (p.Arg45His) (rs180943300)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000171036 SCV000223600 uncertain significance not provided 2019-01-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN1B gene. The R45H variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 3/34418 (0.02%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016). The R45H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support adeleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000559019 SCV000647850 uncertain significance Brugada syndrome 5 2017-06-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 45 of the SCN1B protein (p.Arg45His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs180943300, ExAC 0.009%). This variant has not been reported in the literature in individuals with SCN1B-related disease. ClinVar contains an entry for this variant (Variation ID: 190857). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics,Fulgent Genetics RCV000765438 SCV000896727 uncertain significance Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Epileptic encephalopathy, early infantile, 52 2018-10-31 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.