Genetic Varianta Protein Variantb Variant type Biallelicc Monoallelicd Described
>1 patient
Functional
studiese
Bibliographyf ACMG Classificationg ClinVar ExAC PolyPhen-2 Details
c.9C>A p.Asp3Glu missense - Yes - -     Uncertain
significance
3.3·10-05 Probably
damaging
c.49C>T p.Gln17* nonsense Yes - - Yes     -
c.73G>T p.Glu25* nonsense Yes - Yes Yes     Pathogenic
c.106G>C p.Glu36Gln missense Yes - - Yes     Uncertain
significance
5.8·10-05 Possibly
damaging
c.110del p.Thr37Argfs*26 frameshift Yes - - Yes * Pathogenic
c.145C>T p.Arg49Trp missense - Yes - Yes     Uncertain
significance
Probably
damaging
c.146G>A p.Arg49Gln missense - Yes Yes -     Benign Benign /
Likely
benign
7.6·10-03 Benign
c.173T>C p.Leu58Pro missense Yes - Yes Yes     Likely
pathogenic
Pathogenic 1.7·10-05 Probably
damaging
c.221C>T p.Thr74Met missense - Yes - -     Uncertain
significance
1.1·10-03 Probably
damaging
c.[369_370del;374_376del] p.Val124Glyfs*60 frameshift Yes - Yes Yes * Pathogenic
c.369_370del p.Val124Glyfs*61 frameshift Yes - Yes - * Pathogenic
c.581_584del p.Leu194Profs*3 frameshift Yes - Yes Yes * Pathogenic
c.616G>A p.Glu206Lys missense Yes - - Yes     Uncertain
significance
Uncertain
significance
1.1·10-03 Probably
damaging
c.627C>A p.Ser209Arg missense - Yes - -     Uncertain
significance
Possibly
damaging
c.646C>A p.Arg216Ser missense - Yes - -     Uncertain
significance
1.7·10-05 Benign
c.650T>C p.Leu217Pro missense Yes - - -     Uncertain
significance
Probably
damaging
c.675_679del p.Glu226Leufs*127 frameshift - - - - * Likely
pathogenic
c.687dup p.Gln230Alafs*125 frameshift Yes - Yes Yes * Pathogenic
c.802C>T p.Gln268* nonsense Yes - Yes -     Pathogenic Pathogenic
c.842T>G p.Phe281Cys missense - - - - * Uncertain
significance
4.3·10-05 Benign
g.144140044_144191939del Unknown large
rearrangement
Yes - - Yes * Pathogenic
g.144176890_144196078del Unknown large
rearrangement
Yes - - - * Pathogenic
Genetic Varianta Protein Variantb Variant type Biallelicc Monoallelicd Described
>1 patient
Functional
studiese
Bibliographyf ACMG Classificationg Details
c.9C>A p.Asp3Glu missense - Yes - -     Uncertain
significance
c.49C>T p.Gln17* nonsense Yes - - Yes     -
c.73G>T p.Glu25* nonsense Yes - Yes Yes     Pathogenic
c.106G>C p.Glu36Gln missense Yes - - Yes     Uncertain
significance
c.110del p.Thr37Argfs*26 frameshift Yes - - Yes * Pathogenic
c.145C>T p.Arg49Trp missense - Yes - Yes     Uncertain
significance
c.146G>A p.Arg49Gln missense - Yes Yes -     Benign
c.173T>C p.Leu58Pro missense Yes - Yes Yes     Likely
pathogenic
c.221C>T p.Thr74Met missense - Yes - -     Uncertain
significance
c.[369_370del;374_376del] p.Val124Glyfs*60 frameshift Yes - Yes Yes * Pathogenic
c.369_370del p.Val124Glyfs*61 frameshift Yes - Yes - * Pathogenic
c.581_584del p.Leu194Profs*3 frameshift Yes - Yes Yes * Pathogenic
c.616G>A p.Glu206Lys missense Yes - - Yes     Uncertain
significance
c.627C>A p.Ser209Arg missense - Yes - -     Uncertain
significance
c.646C>A p.Arg216Ser missense - Yes - -     Uncertain
significance
c.650T>C p.Leu217Pro missense Yes - - -     Uncertain
significance
c.675_679del p.Glu226Leufs*127 frameshift - - - - * Likely
pathogenic
c.687dup p.Gln230Alafs*125 frameshift Yes - Yes Yes * Pathogenic
c.802C>T p.Gln268* nonsense Yes - Yes -     Pathogenic
c.842T>G p.Phe281Cys missense - - - - * Uncertain
significance
g.144140044_144191939del Unknown large
rearrangement
Yes - - Yes * Pathogenic
g.144176890_144196078del Unknown large
rearrangement
Yes - - - * Pathogenic

aThe coding DNA reference sequence of genetic variants (c.) is the CDS of ENST00000367568.4, which is equivalent to that of NM_003764.4.
The genomic reference sequence of genetic variants (g.) is the GRCh38 chromosome 6 which is equivalent to NC_000006.12.
bThe protein reference sequence used of protein variants (p.) is ENSP00000356540.4, which is equivalent to NP_003755.2.
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 STX11 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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