ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4052T>C (p.Leu1351Pro) (rs1553525313)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000636329 SCV000757768 likely pathogenic Early infantile epileptic encephalopathy 2018-03-29 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1351 of the SCN1A protein (p.Leu1351Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. 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 focal epilepsy (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant identified in the SCN1A gene is located in the transmembrane spanning D3-S5 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091664 SCV001247839 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing

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