ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.85G>A (p.Glu29Lys)

gnomAD frequency: 0.00001  dbSNP: rs767384862
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000789049 SCV000928323 uncertain significance Childhood absence epilepsy 2019-07-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001222654 SCV001394765 uncertain significance Brugada syndrome 5 2019-06-07 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SCN1B-related conditions. This variant is present in population databases (rs767384862, ExAC 0.009%). This sequence change replaces glutamic acid with lysine at codon 29 of the SCN1B protein (p.Glu29Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine.
Ambry Genetics RCV004027377 SCV003759543 uncertain significance Cardiovascular phenotype 2021-12-12 criteria provided, single submitter clinical testing The c.85G>A (p.E29K) alteration is located in exon 2 (coding exon 2) of the SCN1B gene. This alteration results from a G to A substitution at nucleotide position 85, causing the glutamic acid (E) at amino acid position 29 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV004789188 SCV005400946 uncertain significance Generalized epilepsy with febrile seizures plus, type 1 2023-06-22 criteria provided, single submitter clinical testing The observed missense variant c.85G>A(p.Glu29Lys) in the SCN1B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.001% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Glu at position 29 is changed to a Lys changing protein sequence and it might alter its composition and physico- chemical properties. Multiple lines of computational evidence (Polyphen - Probably damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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