Genetic Varianta Protein Variantb Variant type Biallelicc Monoallelicd Described
>1 patient
Functional
studiese
Bibliographyf ACMG Classificationg ClinVar ExAC PolyPhen-2 Details
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.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.389T>C p.Leu130Ser missense Yes - - Yes     Likely
pathogenic
Uncertain
significance
Probably
damaging
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.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.568C>T p.Arg190Cys missense - Yes - -     Uncertain
significance
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.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.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.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.875G>A p.Arg292His missense Yes - Yes Yes     Likely
pathogenic
8.3·10-06 Probably
damaging
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.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.1066_1074del p.His356_Lys358del in-frame
deletion
Yes - Yes - * Likely
pathogenic
c.1103_1107+4del Unknown splicing Yes - - - * Likely
pathogenic
c.1139A>G p.Glu380Gly missense Yes - - - * - Probably
damaging
c.1172del p.Pro391Argfs*27 frameshift - - - - * Likely
pathogenic
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.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.1697G>A p.Gly566Asp missense Yes - Yes -     Likely
pathogenic
8.2·10-06 Probably
damaging
c.1718C>T p.Pro573Leu missense - - - -     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 Varianta Protein Variantb Variant type Biallelicc Monoallelicd Described
>1 patient
Functional
studiese
Bibliographyf ACMG Classificationg Details
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.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.389T>C p.Leu130Ser missense Yes - - Yes     Likely
pathogenic
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.497C>T p.Thr166Met missense - Yes - - * Likely
benign
c.502dup p.Gln168Profs*71 frameshift Yes - Yes -     Pathogenic
c.568C>T p.Arg190Cys missense - Yes - -     Uncertain
significance
c.575G>A p.Arg192His missense - Yes - -     Uncertain
significance
c.577A>C Unknown splicing Yes - - Yes     Likely
pathogenic
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.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.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.875G>A p.Arg292His missense Yes - Yes Yes     Likely
pathogenic
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.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.1066_1074del p.His356_Lys358del in-frame
deletion
Yes - Yes - * Likely
pathogenic
c.1103_1107+4del Unknown splicing Yes - - - * Likely
pathogenic
c.1139A>G p.Glu380Gly missense Yes - - - * -
c.1172del p.Pro391Argfs*27 frameshift - - - - * Likely
pathogenic
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.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.1697G>A p.Gly566Asp missense Yes - Yes -     Likely
pathogenic
c.1718C>T p.Pro573Leu missense - - - -     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.

Disclaimer: The information on this database is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. The authors are not responsible for neither its use nor misuse. The authors have worked with care in the development of this server, but assume no liability or responsibility for any error, weakness, incompleteness or temporariness of the resource and of the data provided.