Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Bioinformatics, |
RCV000059399 | SCV000221765 | pathogenic | Severe myoclonic epilepsy in infancy | 2014-12-20 | criteria provided, single submitter | research | |
Eurofins Ntd Llc |
RCV000357692 | SCV000344955 | pathogenic | not provided | 2016-08-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000541714 | SCV000633843 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 101 of the SCN1A protein (p.Arg101Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with severe myoclonic epilepsyof infancy (SMEI) and Dravet Syndrome (PMID: 17347258, 20431604, 24168886, 27113213, 27236449). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68527). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SCN1A protein function with a positive predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Arg101 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20431604, 23195492, 23808377, 24328833, 25885068). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000357692 | SCV001249712 | pathogenic | not provided | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV001199316 | SCV001370396 | pathogenic | Migraine, familial hemiplegic, 3 | 2019-05-06 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PP2,PP3,PM2,PM1. |
Lifecell International Pvt. |
RCV000059399 | SCV001738772 | likely pathogenic | Severe myoclonic epilepsy in infancy | criteria provided, single submitter | clinical testing | A heterozygous missense variant (c.301C>T) in exon 5 of the SCN1A gene that results in the amino acid substitution from Arginine to Tryptophan at codon 101 (p.Arg101Trp) was identified. There is a moderate physicochemical difference between Arginine and Tryptophan. The observed variant is not present in both the 1000 Genomes and gnomAD databases. The reference base is conserved across the species and in-silico predictions by Polyphen and SIFT are damaging. The Missense Variants Z-Score for this variant is 5.61. Missense Variants Z-Score is produced by the Exome Aggregation Consortium (60,706 adult humans) by computing a signed Z score for the deviation of observed counts from the expected number. Positive Z scores indicate increased constraint (intolerance to variation) and therefore that the gene had fewer missense variants than expected. (DOI: 10.1038/nature19057). This variant has previously been reported for Dravet syndrome by Usluer S et al., 2016. This variant has been reported to ClinVar as Pathogenic with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 68527 as of 2020-06-04). Based on the above evidence this variant has been classified as Likely pathogenic according to the ACMG guidelines. | |
Gene |
RCV000357692 | SCV002499971 | pathogenic | not provided | 2022-04-05 | criteria provided, single submitter | clinical testing | This substitution is predicted to be within the N-terminal cytoplasmic domain; Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19585586, 20431604, 26096185, 27113213, 27236449, 29933521, 17347258, 18930999, 29852413, 30619928, 31164858, 31864146, 32090326, 29573403, 33278787, 31031587) |
Institute of Human Genetics, |
RCV000059399 | SCV004812080 | pathogenic | Severe myoclonic epilepsy in infancy | 2024-08-30 | criteria provided, single submitter | clinical testing | Criteria applied: PM5_STR,PS2_MOD,PS4_MOD,PM2_SUP,PP2,PP3 |
Uni |
RCV000059399 | SCV000090923 | not provided | Severe myoclonic epilepsy in infancy | no assertion provided | not provided |