ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5010_5013del (p.Phe1671fs) (rs794726754)

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Total submissions: 5
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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 2018-11-06 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SCN1A gene (p.Phe1671Thrfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 339 amino acids of the SCN1A protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with Dravet syndrome and early infantile epileptic encephalopathy (PMID: 11359211, 26993267). ClinVar contains an entry for this variant (Variation ID: 189914). This variant disrupts the C-terminus of the SCN1A protein. Other variant(s) that disrupt this region ( p.Lys1846Serfs*11, p.Arg1886*) have been determined to be pathogenic (PMID: 11359211, 14504318, 21719429, 17054684, 18930999). This suggests that variants that disrupt this region of the protein are likely to be causative of disease 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 2021-08-11 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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