Submissions for variant NM_001165963.4(SCN1A):c.314C>T (p.Thr105Ile)

dbSNP: rs796053089

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189071	SCV000242702	pathogenic	not provided	2015-01-07	criteria provided, single submitter	clinical testing	p.Thr105Ile (ACC>ATC): c.314 C>T in exon 2 of the SCN1A gene (NM_001165963.1) The T105I missense mutation in the SCN1A gene has been reported previously in an individual with severe myoclonic epilepsy of infancy (SMEI) (Wang et al., 2012). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. T105I is a non-conservative amino acid substitution that alters a conserved position in the N-terminal region of the SCN1A protein. Additionally, several other missense mutations affecting nearby residues (S103G, A104V, S106F, L108R) have been reported in association with SCN1A-related disorders in an external mutation database, supporting the functional importance of this region of the SCN1A protein. Therefore, the presence of the T105I mutation is consistent with a diagnosis of a SCN1A-related disorder. The variant is found in INFANTV2-EPIV2-1 panel(s).
CeGaT Center for Human Genetics Tuebingen	RCV000189071	SCV001501318	likely pathogenic	not provided	2020-09-01	criteria provided, single submitter	clinical testing