ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.5844G>T (p.Met1948Ile) (rs763997333)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000488105 SCV000575244 uncertain significance not provided 2016-11-30 criteria provided, single submitter clinical testing
Invitae RCV000703835 SCV000832757 uncertain significance Early infantile epileptic encephalopathy 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 1959 of the SCN1A protein (p.Met1959Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs763997333, ExAC 0.006%). This variant has not been reported in the literature in individuals with SCN1A-related disease. ClinVar contains an entry for this variant (Variation ID: 425223). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 cytoplasmic C-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.

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