Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV001255853 | SCV001432294 | pathogenic | Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 | 2020-06-11 | criteria provided, single submitter | clinical testing | The c.1133delT variant is not present in publicly available databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP. The variant is not present in our in-house exome database. The variant was earlier not reported to ClinVar, OMIM and Human Genome Mutation Database (HGMD) in any affected individuals. However a missense variant was reported earlier to HGMD (ID:CM096127) in the same position in similarly affected individuals [Depienne et al., J Med Genet 2009]. In-silico pathogenicity prediction programs like MutationTaster2, CADD etc. predicted this variant to be likely deleterious. The variant causes a frameshift at 378th amino acid position that creates stop codon at 379thamino acid position of the altered transcript. This may either cause a nonsense mediated decay of the mRNA resulting in no protein or a truncated protein due to premature stop codon. The variant meets the criteria of ACMG guidelines to be classified as 'Pathogenic'. |
| Lifecell International Pvt. |
RCV001528186 | SCV001739368 | likely pathogenic | Severe myoclonic epilepsy in infancy | criteria provided, single submitter | clinical testing | A heterozygous one-base deletion in exon 11 of the SCN1A gene (c.1133delT) that results in a frameshift and premature truncation of the protein 2 amino acids downstream to codon 378 (p.Leu378GlnfsTer2) was detected. This frameshift variant is not reported in both the 1000 genomes and gnomAD databases. The gene has a low rate of benign loss of function variants as indicated by a high LoF variants Z-Score of 7.90. The variant is a loss of function variant in the gene, which is intolerant of Loss of Function variants, as indicated by the presence of existing pathogenic loss of function variant NP_001159435.1:p.M1I and 443 others. There are 341 downstream pathogenic loss of function variants, with the furthest variant being 1548 residues downstream of the variant. Based on the above evidence this variant has been classified as Likely pathogenic according to the ACMG guidelines. |