Submissions for variant NM_001165963.4(SCN1A):c.751A>G (p.Met251Val)

dbSNP: rs2105890375

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV001823483	SCV002072951	uncertain significance	Generalized epilepsy with febrile seizures plus, type 2		criteria provided, single submitter	clinical testing	The missense variant p.M251V in SCN1A (NM_001165963.4) has not been reported previously as a pathogenic nor a benign variant to the best of our knowledge. Another missense mutation affecting the same residue M251R has been previously reported to be disease causing. The p.M251V variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.M251V missense variant is predicted to be damaging by both SIFT and PolyPhen2. The methionine residue at codon 251 of SCN1A is conserved in all mammalian species. The nucleotide c.751 in SCN1A is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Department of Neurology, Zibo Changguo Hospital	RCV005242105	SCV005889660	likely pathogenic	Generalized epilepsy with febrile seizures plus, type 2; Developmental and epileptic encephalopathy 6B	2025-01-09	criteria provided, single submitter	clinical testing	PM1, PM2_Supporting, PM5, PP2, PP3_Moderate