Submissions for variant NM_006922.4(SCN3A):c.3998C>T (p.Pro1333Leu)

dbSNP: rs1057520753

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000420271	SCV000517296	pathogenic	not provided	2015-05-19	criteria provided, single submitter	clinical testing	The P1333L variant in the SCN3A gene has not been reported previously as a pathogenic variantnor as a benign polymorphism, to our knowledge. The P1333L substitution was not observed in approximately6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The P1333L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residuesdiffer in some properties. This substitution occurs at a position that is conserved across species. In silicoanalysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (M1323V) has been reported in association with focal epilepsy (Vanoye et al., 2014),supporting the functional importance of this region of the protein. Therefore, we interpret the P1333L variant as pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000625713	SCV002044410	likely pathogenic	Developmental and epileptic encephalopathy, 62	2021-12-21	criteria provided, single submitter	research
OMIM	RCV000625713	SCV000746213	pathogenic	Developmental and epileptic encephalopathy, 62	2020-11-17	no assertion criteria provided	literature only
Channelopathy-Associated Epilepsy Research Center	RCV003992291	SCV004809316	not provided	Early infantile epileptic encephalopathy with suppression bursts		no assertion provided	literature only