STXBP2

see figure with all variants

Genetic Variant^a	Protein Variant^b	Variant type	Biallelic^c	Monoallelic^d	Described >1 patient	Functional studies^e	Bibliography^f	ACMG Classification^g	ClinVar	ExAC	PolyPhen-2
c.37+5G>A	Unknown	splicing	Yes	-	-	-		Uncertain significance
c.38_87del	p.Lys13Serfs*24	frameshift	Yes	-	-	-	*	Pathogenic
c.56T>C	p.Ile19Thr	missense	-	Yes	-	-		Uncertain significance			Probably damaging
c.87+2T>C	Unknown	splicing	Yes	-	-	-		Pathogenic
c.88-1G>A	Unknown	splicing	Yes	-	-	Yes		Pathogenic
c.116G>C	p.Arg39Pro	missense	Yes	-	-	-		Uncertain significance			Probably damaging
c.184A>G	p.Asn62Asp	missense	Yes	Yes	Yes	-		Uncertain significance		5.1·10^-05	Possibly damaging
c.190C>T	p.Arg64Trp	missense	-	Yes	-	-		Uncertain significance		3.4·10^-05	Probably damaging
c.193C>T	p.Arg65Trp	missense	-	Yes	-	Yes		Likely pathogenic			Probably damaging
c.194G>A	p.Arg65Gln	missense	-	Yes	-	Yes		Likely pathogenic		3.4·10^-05	Probably damaging
c.224_227del	p.Tyr75Cysfs*2	frameshift	Yes	-	-	-	*	Pathogenic
c.260del	p.Leu87Argfs*32	frameshift	-	-	Yes	-	*	Pathogenic	Pathogenic
c.279del	p.Thr94Profs*25	frameshift	Yes	-	-	-	*	Pathogenic
c.301_303del	p.Ala101del	in-frame deletion	Yes	-	-	Yes	*	Pathogenic
c.310A>T	p.Ile104Phe	missense	Yes	-	-	-		Uncertain significance			Possibly damaging
c.326-23_326-16del	Unknown	splicing	Yes	-	-	Yes	*	Likely pathogenic
c.326-30_326-23del	Unknown	deep-intronic	Yes	-	-	-		-
c.359G>A	p.Arg120His	missense	-	Yes	-	-		Uncertain significance		8.2·10^-06	Benign
c.389T>C	p.Leu130Ser	missense	Yes	-	-	Yes		Likely pathogenic	Uncertain significance		Probably damaging
c.390_392del	p.Lys131del	in-frame deletion	-	Yes	-	-		Uncertain significance
c.395A>C	p.Glu132Ala	missense	Yes	-	-	Yes		Likely pathogenic			Probably damaging
c.416C>G	p.Pro139Arg	missense	Yes	-	-	Yes		Likely pathogenic			Probably damaging
c.430-1G>A	Unknown	splicing	Yes	-	Yes	Yes		-
c.474_483delinsGA	p.Cys158Trpfs*78	frameshift	Yes	-	Yes	Yes	*	Pathogenic
c.481del	p.Arg161Glyfs*49	frameshift	Yes	-	Yes	-	*	Pathogenic
c.495C>T	p.Arg165=	silent	-	Yes	-	-	*	Benign	Benign / Likely benign	1.0·10^-02
c.497C>T	p.Thr166Met	missense	-	Yes	-	-		Likely benign	Likely benign	2.5·10^-04	Benign
c.502dup	p.Gln168Profs*71	frameshift	Yes	-	Yes	-		Pathogenic
c.539_540delinsAA	p.Cys180*	nonsense	Yes	-	-	-	*	-
c.560C>T	p.Pro187Leu	missense	Yes	-	-	-		Uncertain significance			Probably damaging
c.568C>T	p.Arg190Cys	missense	-	Yes	Yes	Yes		Likely pathogenic	Uncertain significance	6.7·10^-04	Probably damaging
c.575G>A	p.Arg192His	missense	-	Yes	-	-		Uncertain significance			Probably damaging
c.577A>C	Unknown	splicing	Yes	-	-	Yes		Likely pathogenic
c.610G>C	p.Ala204Pro	missense	Yes	-	-	-	*	Uncertain significance			Probably damaging
c.626T>C	p.Leu209Pro	missense	Yes	-	Yes	Yes		Likely pathogenic	Pathogenic		Probably damaging
c.663G>C	p.Glu221Asp	missense	Yes	-	-	-		-			Possibly damaging
c.693_695del	p.Ile232del	in-frame deletion	Yes	-	Yes	Yes	*	Likely pathogenic	Pathogenic
c.703C>G	p.Arg235Gly	missense	Yes	-	-	-		Likely pathogenic			Probably damaging
c.704G>C	p.Arg235Pro	missense	-	Yes	-	-		Uncertain significance			Probably damaging
c.704G>T	p.Arg235Leu	missense	Yes	-	-	-		Uncertain significance			Probably damaging
c.706del	p.Ala236Glnfs*24	frameshift	Yes	-	Yes	-	*	Pathogenic	Pathogenic
c.715C>T	p.Pro239Ser	missense	-	Yes	-	-		Uncertain significance			Probably damaging
c.728T>G	p.Leu243Arg	missense	Yes	-	-	Yes		-			Probably damaging
c.752C>T	p.Ala251Val	missense	Yes	-	-	-		Likely pathogenic			Probably damaging
c.767T>C	p.Leu256Pro	missense	-	Yes	-	-		Uncertain significance			Probably damaging
c.769_771del	p.Leu257del	in-frame deletion	Yes	-	-	-	*	Likely pathogenic
c.781C>T	p.Gln261*	nonsense	Yes	-	-	-		Pathogenic
c.795-4C>T	Unknown	splicing	Yes	Yes	Yes	-		Benign	Benign / Likely benign	1.3·10^-02
c.862T>C	p.Trp288Arg	missense	Yes	-	-	-		Uncertain significance			Probably damaging
c.875G>A	p.Arg292His	missense	Yes	-	Yes	Yes		Likely pathogenic		8.3·10^-06	Probably damaging
c.902+2del	Unknown	splicing	Yes	-	-	-		-
c.902+5G>A	Unknown	splicing	Yes	-	Yes	-		Likely pathogenic		6.6·10^-05
c.902+6T>G	Unknown	splicing	Yes	-	-	-		Uncertain significance
c.911C>T	p.Thr304Met	missense	-	Yes	-	-		Uncertain significance		1.2·10^-04	Probably damaging
c.953C>T	p.Thr318Met	missense	-	Yes	-	-		Uncertain significance		3.8·10^-04	Probably damaging
c.971A>G	p.Lys324Arg	missense	Yes	-	-	-		Uncertain significance		8.2·10^-06	Benign
c.1001C>T	p.Pro334Leu	missense	Yes	-	Yes	Yes		Likely pathogenic		4.9·10^-05	Probably damaging
c.1034C>T	p.Thr345Met	missense	Yes	Yes	Yes	-		Likely pathogenic	Benign / Likely benign	1.1·10^-02	Probably damaging
c.1057T>C	p.Cys353Arg	missense	Yes	-	-	-		Uncertain significance		8.3·10^-06	Probably damaging
c.1066_1074del	p.His356_Lys358del	in-frame deletion	Yes	-	Yes	-	*	Likely pathogenic
c.1103_1107+4del	Unknown	splicing	Yes	-	-	-	*	Likely pathogenic
c.1106A>G	p.Gln369Arg	missense	Yes	-	-	-	*	Pathogenic			Probably damaging
c.1139A>G	p.Glu380Gly	missense	Yes	-	-	-	*	-			Probably damaging
c.1172del	p.Pro391Argfs*27	frameshift	-	-	-	-	*	Likely pathogenic
c.1204G>A	p.Asp402Asn	missense	-	Yes	-	-		Uncertain significance		1.5·10^-04	Probably damaging
c.1213C>G	p.Arg405Gly	missense	Yes	Yes	Yes	-	*	Likely pathogenic			Probably damaging
c.1213C>T	p.Arg405Trp	missense	-	-	Yes	Yes		Pathogenic		8.4·10^-06	Probably damaging
c.1214G>A	p.Arg405Gln	missense	Yes	-	Yes	Yes	*	Pathogenic	Pathogenic	1.7·10^-05	Probably damaging
c.1247-1G>C	Unknown	splicing	Yes	-	Yes	Yes		Pathogenic	Pathogenic	3.3·10^-04
c.1252_1255del	p.Ser418Argfs*7	frameshift	Yes	-	-	Yes	*	Pathogenic
c.1294C>T	p.Gln432*	nonsense	Yes	-	-	Yes		Pathogenic
c.1298C>T	p.Ala433Val	missense	-	Yes	-	-		Benign	Benign / Likely benign	1.6·10^-02	Benign
c.1356+1G>A	Unknown	splicing	Yes	-	Yes	-		Pathogenic
c.1375C>T	p.Arg459Trp	missense	-	Yes	-	-		Benign	Likely benign	6.0·10^-03	Probably damaging
c.1430C>T	p.Pro477Leu	missense	Yes	-	Yes	Yes		Pathogenic	Pathogenic		Probably damaging
c.1444G>A	p.Val482Ile	missense	-	Yes	-	-		Likely benign		2.8·10^-05	Benign
c.1452+1G>A	Unknown	splicing	Yes	-	-	-		Pathogenic
c.1459G>A	p.Val487Met	missense	-	Yes	-	-		Uncertain significance		5.1·10^-04	Probably damaging
c.1586G>C	p.Arg529Pro	missense	-	Yes	-	-		Uncertain significance	Conflicting interpretations pathogenicity	1.6·10^-03	Probably damaging
c.1601T>C	p.Leu534Pro	missense	Yes	-	-	-		Likely pathogenic			Probably damaging
c.1621G>A	p.Gly541Ser	missense	Yes	-	Yes	Yes		Likely pathogenic	Pathogenic / Likely pathogenic	2.4·10^-04	Probably damaging
c.1634C>T	p.Ser545Leu	missense	Yes	-	-	Yes		Pathogenic			Possibly damaging
c.1663A>G	p.Arg555Gly	missense	-	Yes	-	-	*	Benign	Benign	4.3·10^-03	Benign
c.1696+1G>A	Unknown	splicing	Yes	-	Yes	-		Pathogenic
c.1696+5G>T	Unknown	splicing	Yes	-	-	-		-
c.1697G>A	p.Gly566Asp	missense	Yes	-	-	-	*	Pathogenic		8.2·10^-06	Probably damaging
c.1717C>T	p.Pro573Ser	missense	Yes	-	-	-		Uncertain significance			Probably damaging
c.1718C>T	p.Pro573Leu	missense	Yes	-	-	-		Uncertain significance		2.5·10^-05	Probably damaging
c.1724_1729del	p.Arg575_Phe576del	in-frame deletion	Yes	-	-	-	*	Likely pathogenic
c.1726T>C	p.Phe576Leu	missense	-	Yes	-	-		Uncertain significance			Possibly damaging
c.1727del	p.Phe576Serfs*5	frameshift	Yes	-	Yes	-	*	Pathogenic

Genetic Variant^a	Protein Variant^b	Variant type	Biallelic^c	Monoallelic^d	Described >1 patient	Functional studies^e	Bibliography^f	ACMG Classification^g
c.37+5G>A	Unknown	splicing	Yes	-	-	-		Uncertain significance
c.38_87del	p.Lys13Serfs*24	frameshift	Yes	-	-	-	*	Pathogenic
c.56T>C	p.Ile19Thr	missense	-	Yes	-	-		Uncertain significance
c.87+2T>C	Unknown	splicing	Yes	-	-	-		Pathogenic
c.88-1G>A	Unknown	splicing	Yes	-	-	Yes		Pathogenic
c.116G>C	p.Arg39Pro	missense	Yes	-	-	-		Uncertain significance
c.184A>G	p.Asn62Asp	missense	Yes	Yes	Yes	-		Uncertain significance
c.190C>T	p.Arg64Trp	missense	-	Yes	-	-		Uncertain significance
c.193C>T	p.Arg65Trp	missense	-	Yes	-	Yes		Likely pathogenic
c.194G>A	p.Arg65Gln	missense	-	Yes	-	Yes		Likely pathogenic
c.224_227del	p.Tyr75Cysfs*2	frameshift	Yes	-	-	-	*	Pathogenic
c.260del	p.Leu87Argfs*32	frameshift	-	-	Yes	-	*	Pathogenic
c.279del	p.Thr94Profs*25	frameshift	Yes	-	-	-	*	Pathogenic
c.301_303del	p.Ala101del	in-frame deletion	Yes	-	-	Yes	*	Pathogenic
c.310A>T	p.Ile104Phe	missense	Yes	-	-	-		Uncertain significance
c.326-23_326-16del	Unknown	splicing	Yes	-	-	Yes	*	Likely pathogenic
c.326-30_326-23del	Unknown	deep-intronic	Yes	-	-	-		-
c.359G>A	p.Arg120His	missense	-	Yes	-	-		Uncertain significance
c.389T>C	p.Leu130Ser	missense	Yes	-	-	Yes		Likely pathogenic
c.390_392del	p.Lys131del	in-frame deletion	-	Yes	-	-		Uncertain significance
c.395A>C	p.Glu132Ala	missense	Yes	-	-	Yes		Likely pathogenic
c.416C>G	p.Pro139Arg	missense	Yes	-	-	Yes		Likely pathogenic
c.430-1G>A	Unknown	splicing	Yes	-	Yes	Yes		-
c.474_483delinsGA	p.Cys158Trpfs*78	frameshift	Yes	-	Yes	Yes	*	Pathogenic
c.481del	p.Arg161Glyfs*49	frameshift	Yes	-	Yes	-	*	Pathogenic
c.495C>T	p.Arg165=	silent	-	Yes	-	-	*	Benign
c.497C>T	p.Thr166Met	missense	-	Yes	-	-		Likely benign
c.502dup	p.Gln168Profs*71	frameshift	Yes	-	Yes	-		Pathogenic
c.539_540delinsAA	p.Cys180*	nonsense	Yes	-	-	-	*	-
c.560C>T	p.Pro187Leu	missense	Yes	-	-	-		Uncertain significance
c.568C>T	p.Arg190Cys	missense	-	Yes	Yes	Yes		Likely pathogenic
c.575G>A	p.Arg192His	missense	-	Yes	-	-		Uncertain significance
c.577A>C	Unknown	splicing	Yes	-	-	Yes		Likely pathogenic
c.610G>C	p.Ala204Pro	missense	Yes	-	-	-	*	Uncertain significance
c.626T>C	p.Leu209Pro	missense	Yes	-	Yes	Yes		Likely pathogenic
c.663G>C	p.Glu221Asp	missense	Yes	-	-	-		-
c.693_695del	p.Ile232del	in-frame deletion	Yes	-	Yes	Yes	*	Likely pathogenic
c.703C>G	p.Arg235Gly	missense	Yes	-	-	-		Likely pathogenic
c.704G>C	p.Arg235Pro	missense	-	Yes	-	-		Uncertain significance
c.704G>T	p.Arg235Leu	missense	Yes	-	-	-		Uncertain significance
c.706del	p.Ala236Glnfs*24	frameshift	Yes	-	Yes	-	*	Pathogenic
c.715C>T	p.Pro239Ser	missense	-	Yes	-	-		Uncertain significance
c.728T>G	p.Leu243Arg	missense	Yes	-	-	Yes		-
c.752C>T	p.Ala251Val	missense	Yes	-	-	-		Likely pathogenic
c.767T>C	p.Leu256Pro	missense	-	Yes	-	-		Uncertain significance
c.769_771del	p.Leu257del	in-frame deletion	Yes	-	-	-	*	Likely pathogenic
c.781C>T	p.Gln261*	nonsense	Yes	-	-	-		Pathogenic
c.795-4C>T	Unknown	splicing	Yes	Yes	Yes	-		Benign
c.862T>C	p.Trp288Arg	missense	Yes	-	-	-		Uncertain significance
c.875G>A	p.Arg292His	missense	Yes	-	Yes	Yes		Likely pathogenic
c.902+2del	Unknown	splicing	Yes	-	-	-		-
c.902+5G>A	Unknown	splicing	Yes	-	Yes	-		Likely pathogenic
c.902+6T>G	Unknown	splicing	Yes	-	-	-		Uncertain significance
c.911C>T	p.Thr304Met	missense	-	Yes	-	-		Uncertain significance
c.953C>T	p.Thr318Met	missense	-	Yes	-	-		Uncertain significance
c.971A>G	p.Lys324Arg	missense	Yes	-	-	-		Uncertain significance
c.1001C>T	p.Pro334Leu	missense	Yes	-	Yes	Yes		Likely pathogenic
c.1034C>T	p.Thr345Met	missense	Yes	Yes	Yes	-		Likely pathogenic
c.1057T>C	p.Cys353Arg	missense	Yes	-	-	-		Uncertain significance
c.1066_1074del	p.His356_Lys358del	in-frame deletion	Yes	-	Yes	-	*	Likely pathogenic
c.1103_1107+4del	Unknown	splicing	Yes	-	-	-	*	Likely pathogenic
c.1106A>G	p.Gln369Arg	missense	Yes	-	-	-	*	Pathogenic
c.1139A>G	p.Glu380Gly	missense	Yes	-	-	-	*	-
c.1172del	p.Pro391Argfs*27	frameshift	-	-	-	-	*	Likely pathogenic
c.1204G>A	p.Asp402Asn	missense	-	Yes	-	-		Uncertain significance
c.1213C>G	p.Arg405Gly	missense	Yes	Yes	Yes	-	*	Likely pathogenic
c.1213C>T	p.Arg405Trp	missense	-	-	Yes	Yes		Pathogenic
c.1214G>A	p.Arg405Gln	missense	Yes	-	Yes	Yes	*	Pathogenic
c.1247-1G>C	Unknown	splicing	Yes	-	Yes	Yes		Pathogenic
c.1252_1255del	p.Ser418Argfs*7	frameshift	Yes	-	-	Yes	*	Pathogenic
c.1294C>T	p.Gln432*	nonsense	Yes	-	-	Yes		Pathogenic
c.1298C>T	p.Ala433Val	missense	-	Yes	-	-		Benign
c.1356+1G>A	Unknown	splicing	Yes	-	Yes	-		Pathogenic
c.1375C>T	p.Arg459Trp	missense	-	Yes	-	-		Benign
c.1430C>T	p.Pro477Leu	missense	Yes	-	Yes	Yes		Pathogenic
c.1444G>A	p.Val482Ile	missense	-	Yes	-	-		Likely benign
c.1452+1G>A	Unknown	splicing	Yes	-	-	-		Pathogenic
c.1459G>A	p.Val487Met	missense	-	Yes	-	-		Uncertain significance
c.1586G>C	p.Arg529Pro	missense	-	Yes	-	-		Uncertain significance
c.1601T>C	p.Leu534Pro	missense	Yes	-	-	-		Likely pathogenic
c.1621G>A	p.Gly541Ser	missense	Yes	-	Yes	Yes		Likely pathogenic
c.1634C>T	p.Ser545Leu	missense	Yes	-	-	Yes		Pathogenic
c.1663A>G	p.Arg555Gly	missense	-	Yes	-	-	*	Benign
c.1696+1G>A	Unknown	splicing	Yes	-	Yes	-		Pathogenic
c.1696+5G>T	Unknown	splicing	Yes	-	-	-		-
c.1697G>A	p.Gly566Asp	missense	Yes	-	-	-	*	Pathogenic
c.1717C>T	p.Pro573Ser	missense	Yes	-	-	-		Uncertain significance
c.1718C>T	p.Pro573Leu	missense	Yes	-	-	-		Uncertain significance
c.1724_1729del	p.Arg575_Phe576del	in-frame deletion	Yes	-	-	-	*	Likely pathogenic
c.1726T>C	p.Phe576Leu	missense	-	Yes	-	-		Uncertain significance
c.1727del	p.Phe576Serfs*5	frameshift	Yes	-	Yes	-	*	Pathogenic

^aThe coding DNA reference sequence of genetic variants (c.) is the CDS of ENST00000221283.10, which is equivalent to that of NM_006949.3.
^bThe protein reference sequence used of protein variants (p.) is ENSP00000221283.4, which is equivalent to NP_008880.2.
^cBiallelic variants include both homozygous and compound heterozygous variants.
^dMonoallelic variants include variants found in one allele. Caution must be exercised in evaluating the role of monoallelic variants since FHL caused by mutations in STXBP2 is essentially an autosomal recessive disease. Most monoallelic variants reported in FHL are not proven to be disease causing by itself but may represent susceptibility in genetic predisposition to FHL.
^eFunctional studies mean that one or more assays (e.g. Western blot, RNA studies, flow cytometry, etc.) have been done to evaluate the functional impact of the variant.
^fBibliography marked with "*" may contain the variant in a different format. Here, we show the variant following the HGVS guidelines.
^gGenetic variants have been classified as pathogenic, likely pathogenic, uncertain significance, likely benign or benign, according to the American College of Medical Genetics (ACMG) guidelines.
- means no supporting information was found.

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