ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.1060G>C (p.Ala354Pro)

dbSNP: rs1698022280
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001219108 SCV001391029 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2019-06-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 354 of the SCN1A protein (p.Ala354Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN1A-related disease. 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 extracellular D1-P1 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.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV001194611 SCV001364264 pathogenic Severe myoclonic epilepsy in infancy 2020-02-19 no assertion criteria provided clinical testing

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