ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5010_5013del (p.Phe1671fs)

dbSNP: rs794726754
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180866 SCV000221831 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000189065 SCV000242696 pathogenic not provided 2014-08-19 criteria provided, single submitter clinical testing c.5010_5013delGTTT: p.Phe1671ThrfsX8 (F1671TfsX8) in exon 26 of the SCN1A gene (NM_001165963.1). The normal sequence with the bases that are deleted in braces is: CGTT{GTTT}AACA. The c.5010_5013delGTTT mutation in the SCN1A gene has been reported previously as a de novo mutation in association with SCN1A-related disorders (Claes et al., 2001; Depienne et al., 2009). The deletion causes a frameshift starting with codon Phenylalanine 1671, changes this amino acid to a Threonine residue and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Phe1671ThrfsX8. This mutation is predicted to cause loss of normal protein function through protein truncation as the last 339 amino acids of the SCN1A protein are replaced with 7 incorrect amino acids. The variant is found in EPILEPSY panel(s).
Invitae RCV000798624 SCV000938249 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2021-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe1671Thrfs*8) in the SCN1A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 339 amino acid(s) of the SCN1A protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Dravet syndrome and early infantile epileptic encephalopathy (PMID: 11359211, 26993267). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 189914). This variant disrupts a region of the SCN1A protein in which other variant(s) (p.Lys1846Serfs*11, p.Arg1886*) have been determined to be pathogenic (PMID: 11359211, 14504318, 17054684, 18930999, 21719429). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000180866 SCV001950118 pathogenic Severe myoclonic epilepsy in infancy 2021-11-19 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PVS1, PS2_VSTR, PS4, PM2_SUP
Genetic Services Laboratory,University of Chicago RCV000189065 SCV002064459 pathogenic not provided 2017-08-11 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003954 SCV001161944 pathogenic Epileptic encephalopathy no assertion criteria provided research

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