ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2522C>T (p.Thr841Met)

gnomAD frequency: 0.00001  dbSNP: rs750901301
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001055611 SCV001220011 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2023-05-16 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 851254). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. This variant is present in population databases (rs750901301, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 841 of the SCN1A protein (p.Thr841Met).
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV001729785 SCV001976727 likely pathogenic Severe myoclonic epilepsy in infancy 2021-08-10 criteria provided, single submitter clinical testing PM1, PM5, PP2, PP3
Ambry Genetics RCV002553797 SCV003554731 likely benign Inborn genetic diseases 2021-08-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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