ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.272T>C (p.Ile91Thr) (rs121918734)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000059474 SCV000221870 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
Invitae RCV000819332 SCV000959986 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2020-02-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 91 of the SCN1A protein (p.Ile91Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with Dravet syndrome (PMID: 18554359). ClinVar contains an entry for this variant (Variation ID: 68597). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant identified in the SCN1A gene is located in the cytoplasmic N-terminal region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. 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.
UniProtKB/Swiss-Prot RCV000059474 SCV000090999 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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