Genetic Varianta Protein Variantb Variant type Biallelicc Monoallelicd Described
>1 patient
Functional
studiese
Bibliographyf ACMG Classificationg ClinVar ExAC PolyPhen-2 Details
c.1A>G p.Met1Val missense Yes - Yes Yes     Pathogenic Possibly
damaging
c.3G>A p.Met1Ile missense Yes - - -     Pathogenic Possibly
damaging
c.10C>T p.Arg4Cys missense Yes Yes Yes -     Uncertain
significance
Uncertain
significance
1.4·10-03 Benign
c.50del p.Leu17Argfs*34 frameshift Yes - Yes Yes * Pathogenic
c.65del p.Pro22Argfs*29 frameshift Yes - Yes - * Pathogenic
c.83G>A p.Arg28His missense - Yes Yes -     Uncertain
significance
Possibly
damaging
c.91T>G p.Cys31Gly missense Yes - - Yes     Pathogenic Probably
damaging
c.93C>G p.Cys31Trp missense Yes - Yes Yes     Pathogenic Probably
damaging
c.98G>A p.Arg33His missense Yes - Yes -     Uncertain
significance
1.1·10-04 Benign
c.112G>A p.Val38Met missense Yes - - -     Likely
pathogenic
Uncertain
significance
7.1·10-05 Probably
damaging
c.116C>A p.Pro39His missense Yes - - Yes     Pathogenic Probably
damaging
c.133G>A p.Gly45Arg missense Yes - - Yes     Pathogenic Uncertain
significance
Probably
damaging
c.134G>A p.Gly45Glu missense Yes - - Yes     Pathogenic Probably
damaging
c.136G>T p.Glu46* nonsense Yes - Yes Yes     Pathogenic
c.140G>T p.Gly47Val missense Yes - Yes Yes     Likely
pathogenic
Probably
damaging
c.145G>A p.Asp49Asn missense Yes - - Yes     Pathogenic Probably
damaging
c.148G>A p.Val50Met missense Yes - - -     Likely
pathogenic
Probably
damaging
c.148G>C p.Val50Leu missense - Yes - -     Likely
pathogenic
6.8·10-05 Possibly
damaging
c.150del p.Thr51Profs*56 frameshift - - - - * Pathogenic
c.160C>T p.Arg54Cys missense Yes - Yes Yes     Pathogenic 3.4·10-05 Probably
damaging
c.185_195del p.Asp62Valfs*12 frameshift Yes - - - * Pathogenic
c.190C>T p.Gln64* nonsense Yes - - -     Pathogenic Pathogenic
c.207del p.Asp70Thrfs*37 frameshift Yes - Yes Yes * Pathogenic
c.208G>T p.Asp70Tyr missense Yes - - Yes     Pathogenic Probably
damaging
c.209A>T p.Asp70Val missense - - - -     Likely
pathogenic
Probably
damaging
c.214A>C p.Thr72Pro missense Yes - - -     Likely
pathogenic
Probably
damaging
c.217T>C p.Cys73Arg missense Yes - - Yes     Pathogenic Probably
damaging
c.218G>A p.Cys73Tyr missense Yes - - - * Likely
pathogenic
8.4·10-06 Probably
damaging
c.265C>A p.Pro89Thr missense Yes - Yes -     Likely
pathogenic
Probably
damaging
c.272C>T p.Ala91Val missense Yes Yes Yes Yes     Uncertain
significance
Conflicting
interpretations
pathogenicity
3.1·10-02 Probably
damaging
c.283T>C p.Trp95Arg missense Yes - - Yes * Pathogenic Probably
damaging
c.284G>A p.Trp95* nonsense Yes - - -     Pathogenic
c.285G>T p.Trp95Cys missense Yes - - Yes     Pathogenic Probably
damaging
c.305G>T p.Cys102Phe missense - Yes Yes -     Likely
pathogenic
8.4·10-06 Probably
damaging
c.350_356delinsATGC p.Val117Aspfs*439 frameshift Yes - - Yes * Pathogenic
c.355C>T p.Arg119Trp missense Yes - Yes Yes     Pathogenic 8.3·10-06 Probably
damaging
c.382G>T p.Asp128Tyr missense Yes - - Yes     Pathogenic Probably
damaging
c.386G>C p.Trp129Ser missense Yes Yes Yes -     Likely
pathogenic
Likely
pathogenic
6.6·10-05 Probably
damaging
c.394G>A p.Gly132Arg missense Yes - Yes Yes     Pathogenic 8.3·10-06 Probably
damaging
c.443C>A p.Ala148Asp missense Yes - - Yes     Pathogenic 1.6·10-05 Probably
damaging
c.445G>A p.Gly149Ser missense Yes - - Yes     Likely
pathogenic
Pathogenic 1.4·10-04 Probably
damaging
c.445G>C p.Gly149Arg missense Yes - Yes Yes     Pathogenic Probably
damaging
c.449C>A p.Ser150* nonsense Yes - - Yes     Pathogenic 2.5·10-05
c.452A>T p.His151Leu missense Yes - - -     Likely
pathogenic
8.2·10-06 Probably
damaging
c.469T>G p.Phe157Val missense Yes - - Yes     Pathogenic Probably
damaging
c.490C>T p.Gln164* nonsense Yes - - Yes     Pathogenic
c.503G>A p.Ser168Asn missense - - - - * Uncertain
significance
2.5·10-05 Benign
c.508A>C p.Ser170Arg missense Yes - - Yes     Pathogenic Possibly
damaging
c.512C>A p.Thr171Asn missense Yes - - Yes     Likely
pathogenic
Benign
c.528_529delinsAA p.Cys176* nonsense Yes - Yes Yes * Pathogenic
c.548T>G p.Val183Gly missense Yes - - Yes     Pathogenic Pathogenic Possibly
damaging
c.563C>T p.Pro188Leu missense Yes - - Yes     Likely
pathogenic
1.1·10-04 Probably
damaging
c.577T>C p.Phe193Leu missense Yes - - Yes     Pathogenic Probably
damaging
c.590T>G p.Leu197Arg missense Yes - - Yes     Pathogenic Probably
damaging
c.601C>A p.Pro201Thr missense Yes - Yes Yes     Pathogenic Probably
damaging
c.614A>G p.Asn205Ser missense Yes - - Yes     Pathogenic 2.5·10-05 Probably
damaging
c.626A>C p.Gln209Pro missense Yes - - Yes     Likely
pathogenic
1.7·10-05 Possibly
damaging
c.632C>T p.Ala211Val missense - Yes Yes -     Likely
benign
Benign 2.4·10-03 Benign
c.643C>A p.Leu215Ile missense Yes - - Yes     Pathogenic Probably
damaging
c.655T>A p.Tyr219Asn missense - Yes - Yes     Likely
pathogenic
Probably
damaging
c.657C>A p.Tyr219* nonsense Yes - - -     Pathogenic 8.3·10-06
c.658G>A p.Gly220Ser missense Yes - Yes Yes     Pathogenic 8.3·10-06 Probably
damaging
c.658G>C p.Gly220Arg missense Yes - - Yes     Pathogenic Probably
damaging
c.659G>A p.Gly220Asp missense Yes - - -     Pathogenic 1.7·10-05 Probably
damaging
c.662C>T p.Thr221Ile missense Yes - - Yes     Pathogenic Probably
damaging
c.665A>G p.His222Arg missense Yes Yes Yes Yes     Pathogenic Probably
damaging
c.666C>A p.His222Gln missense Yes - Yes Yes     Pathogenic Pathogenic 2.5·10-05 Probably
damaging
c.671T>A p.Ile224Asn missense Yes - Yes -     Likely
pathogenic
Probably
damaging
c.673C>T p.Arg225Trp missense Yes - Yes Yes     Pathogenic Pathogenic 2.5·10-05 Probably
damaging
c.674G>C p.Arg225Pro missense Yes - Yes Yes     Pathogenic Uncertain
significance
Possibly
damaging
c.694C>T p.Arg232Cys missense Yes - - Yes     Pathogenic 1.7·10-05 Probably
damaging
c.695G>A p.Arg232His missense Yes - - Yes     Uncertain
significance
Uncertain
significance
9.1·10-05 Probably
damaging
c.718C>G p.Arg240Gly missense Yes - - -     Likely
pathogenic
Probably
damaging
c.727G>T p.Glu243* nonsense Yes - - Yes     Pathogenic
c.755A>G p.Asn252Ser missense Yes Yes Yes Yes     Uncertain
significance
Conflicting
interpretations
pathogenicity
5.2·10-03 Benign
c.757G>A p.Glu253Lys missense Yes - Yes Yes     Likely
pathogenic
3.3·10-05 Probably
damaging
c.781G>A p.Glu261Lys missense Yes - - Yes     Pathogenic 8.2·10-06 Probably
damaging
c.785C>A p.Ala262Asp missense Yes - - Yes     Pathogenic Probably
damaging
c.785C>T p.Ala262Val missense Yes - - Yes     Pathogenic Probably
damaging
c.786_801del p.Gln263Serfs*21 frameshift Yes - - - * Pathogenic
c.797T>C p.Ile266Thr missense Yes - - Yes     Likely
pathogenic
8.2·10-06 Probably
damaging
c.833C>A p.Ala278Asp missense - Yes - Yes     Likely
pathogenic
Possibly
damaging
c.836G>A p.Cys279Tyr missense Yes - - Yes     Pathogenic Pathogenic 3.3·10-05 Probably
damaging
c.851_862del p.Lys284_Lys287del in-frame
deletion
Yes - - Yes * Likely
pathogenic
c.853_855del p.Lys285del in-frame
deletion
Yes - Yes Yes * Likely
pathogenic
c.879del p.Gln294Lysfs*36 frameshift Yes - - - * Pathogenic
c.886T>C p.Tyr296His missense Yes - Yes Yes     Pathogenic 1.6·10-05 Probably
damaging
c.893A>G p.Glu298Gly missense Yes - - Yes     Pathogenic Probably
damaging
c.895C>A p.Arg299Ser missense Yes - - Yes     Pathogenic Probably
damaging
c.895C>T p.Arg299Cys missense Yes - - -     Likely
pathogenic
Probably
damaging
c.902C>A p.Ser301* nonsense Yes - - -     Pathogenic
c.916G>A p.Gly306Ser missense Yes - Yes Yes     Likely
pathogenic
Uncertain
significance
2.5·10-05 Probably
damaging
c.916G>T p.Gly306Cys missense Yes - Yes Yes     Pathogenic Probably
damaging
c.938A>T p.Asp313Val missense Yes - - -     Likely
pathogenic
1.6·10-05 Probably
damaging
c.941_948delinsA p.Leu314Glnfs*14 frameshift Yes - - Yes * Pathogenic
c.949G>A p.Gly317Arg missense Yes - - -     Likely
pathogenic
1.6·10-05 Probably
damaging
c.992C>T p.Ser331Leu missense - Yes - Yes     Likely
pathogenic
Uncertain
significance
1.7·10-05 Probably
damaging
c.1000G>A p.Gly334Ser missense - - - -     Uncertain
significance
Uncertain
significance
3.9·10-04 Benign
c.1018G>A p.Asp340Asn missense Yes - - Yes     Pathogenic 8.3·10-06 Possibly
damaging
c.1034C>G p.Pro345Arg missense Yes - - -     Likely
pathogenic
Probably
damaging
c.1034C>T p.Pro345Leu missense Yes - - -     Likely
pathogenic
Pathogenic 8.4·10-06 Probably
damaging
c.1042G>A p.Val348Met missense Yes Yes Yes -     Uncertain
significance
8.4·10-06 Benign
c.1066C>T p.Arg356Trp missense Yes - - Yes     Pathogenic 8.6·10-06 Benign
c.1081A>T p.Arg361Trp missense Yes - - Yes     Pathogenic Pathogenic 8.7·10-06 Probably
damaging
c.1083del p.Arg362Glyfs*3 frameshift Yes - - - * Pathogenic
c.1090_1091del p.Leu364Glufs*93 frameshift Yes - Yes - * Pathogenic
c.1091T>G p.Leu364Arg missense Yes - - Yes     Pathogenic Probably
damaging
c.1099T>C p.Tyr367His missense Yes - - Yes     Pathogenic Probably
damaging
c.1120T>G p.Trp374Gly missense Yes - - -     Likely
pathogenic
Likely
pathogenic
Probably
damaging
c.1122G>A p.Trp374* nonsense Yes - Yes Yes     Pathogenic Pathogenic 8.8·10-06
c.1122G>T p.Trp374Cys missense Yes - - -     Likely
pathogenic
Benign
c.1146_1168del p.Pro383Argfs*67 frameshift - - - - * Likely
pathogenic
c.1168C>T p.Arg390* nonsense - Yes - -     Pathogenic 8.7·10-06
c.1177T>C p.Cys393Arg missense Yes - - -     Likely
pathogenic
Probably
damaging
c.1179C>A p.Cys393* nonsense Yes - - -     Pathogenic
c.1181_1182insT p.Gln394Hisfs*64 frameshift Yes - - Yes * Pathogenic
c.1183T>C p.Cys395Arg missense Yes - - Yes     Pathogenic Probably
damaging
c.1189_1190dup p.His398Alafs*23 frameshift Yes - Yes Yes * Pathogenic
c.1220G>A p.Cys407Tyr missense Yes - - Yes     Likely
pathogenic
Probably
damaging
c.1226C>A p.Pro409His missense Yes - - Yes     Likely
pathogenic
Probably
damaging
c.1228C>T p.Arg410Trp missense Yes - - Yes     Likely
pathogenic
5.1·10-05 Probably
damaging
c.1229G>A p.Arg410Gln missense - Yes - Yes     Uncertain
significance
5.2·10-04 Possibly
damaging
c.1243G>A p.Ala415Thr missense Yes - - Yes     Likely
pathogenic
Probably
damaging
c.1246C>T p.Gln416* nonsense Yes - - Yes     Pathogenic Pathogenic 8.5·10-06
c.1283G>A p.Trp428* nonsense - - - -     Pathogenic
c.1284G>A p.Trp428* nonsense - - - -     Pathogenic
c.1284G>C p.Trp428Cys missense Yes - - -     Uncertain
significance
Probably
damaging
c.1286G>A p.Gly429Glu missense Yes - - Yes     Likely
pathogenic
Pathogenic Probably
damaging
c.1288dup p.Asp430Glyfs*28 frameshift Yes - Yes Yes     Pathogenic
c.1288G>A p.Asp430Asn missense Yes - - Yes     Likely
pathogenic
Probably
damaging
c.1288G>T p.Asp430Tyr missense Yes - Yes Yes     Likely
pathogenic
Probably
damaging
c.1297A>C p.Thr433Pro missense - - - -     Uncertain
significance
Probably
damaging
c.1304C>T p.Thr435Met missense Yes - Yes Yes     Pathogenic Pathogenic 1.7·10-05 Probably
damaging
c.1310C>T p.Ala437Val missense - Yes - Yes     Uncertain
significance
Conflicting
interpretations
pathogenicity
8.1·10-04 Probably
damaging
c.1313A>G p.Tyr438Cys missense - - - -     Uncertain
significance
Uncertain
significance
8.3·10-06 Probably
damaging
c.1314T>A p.Tyr438* nonsense Yes - - -     Pathogenic
c.1337A>C p.Gln446Pro missense Yes - Yes Yes     Likely
pathogenic
Likely
pathogenic
8.3·10-06 Possibly
damaging
c.1337A>G p.Gln446Arg missense - - - -     Uncertain
significance
Benign
c.1349C>T p.Thr450Met missense Yes Yes Yes Yes     Pathogenic Likely
pathogenic
5.0·10-05 Probably
damaging
c.1361G>A p.Trp454* nonsense - - - -     Pathogenic
c.1376C>T p.Pro459Leu missense Yes - Yes Yes     Uncertain
significance
Probably
damaging
c.1385C>A p.Ser462* nonsense Yes - - Yes     Pathogenic Pathogenic
c.1423del p.Leu478* nonsense Yes - - - * Pathogenic
c.1433T>G p.Leu478Arg missense Yes - - -     Likely
pathogenic
Probably
damaging
c.1442A>C p.Gln481Pro missense Yes Yes Yes Yes     Pathogenic 8.2·10-06 Probably
damaging
c.1450G>A p.Asp484Asn missense Yes - - - * Likely
pathogenic
8.2·10-06 Probably
damaging
c.1450G>T p.Asp484Tyr missense Yes - - -     Likely
pathogenic
Probably
damaging
c.1451del p.Asp484Valfs*25 frameshift Yes - - Yes * Pathogenic
c.1465A>T p.Arg489Trp missense - Yes - -     Uncertain
significance
Benign
c.1471G>A p.Asp491Asn missense Yes Yes Yes Yes     Likely
pathogenic
Probably
damaging
c.1491T>A p.Cys497* nonsense Yes - - -     Pathogenic
c.1535T>G p.Leu512Arg missense Yes - - - * Uncertain
significance
Probably
damaging
c.1568C>A p.Ala523Asp missense Yes - - -     Uncertain
significance
Probably
damaging
c.1574G>C p.Cys525Ser missense - - - -     Uncertain
significance
Probably
damaging
c.1577del p.Leu526Cysfs*87 frameshift Yes - - - * Likely
pathogenic
c.1628dup p.Glu545Glyfs*41 frameshift Yes - - Yes * Pathogenic
c.1637del p.Pro546Leufs*67 frameshift Yes - - Yes * Pathogenic
Genetic Varianta Protein Variantb Variant type Biallelicc Monoallelicd Described
>1 patient
Functional
studiese
Bibliographyf ACMG Classificationg Details
c.1A>G p.Met1Val missense Yes - Yes Yes     Pathogenic
c.3G>A p.Met1Ile missense Yes - - -     Pathogenic
c.10C>T p.Arg4Cys missense Yes Yes Yes -     Uncertain
significance
c.50del p.Leu17Argfs*34 frameshift Yes - Yes Yes * Pathogenic
c.65del p.Pro22Argfs*29 frameshift Yes - Yes - * Pathogenic
c.83G>A p.Arg28His missense - Yes Yes -     Uncertain
significance
c.91T>G p.Cys31Gly missense Yes - - Yes     Pathogenic
c.93C>G p.Cys31Trp missense Yes - Yes Yes     Pathogenic
c.98G>A p.Arg33His missense Yes - Yes -     Uncertain
significance
c.112G>A p.Val38Met missense Yes - - -     Likely
pathogenic
c.116C>A p.Pro39His missense Yes - - Yes     Pathogenic
c.133G>A p.Gly45Arg missense Yes - - Yes     Pathogenic
c.134G>A p.Gly45Glu missense Yes - - Yes     Pathogenic
c.136G>T p.Glu46* nonsense Yes - Yes Yes     Pathogenic
c.140G>T p.Gly47Val missense Yes - Yes Yes     Likely
pathogenic
c.145G>A p.Asp49Asn missense Yes - - Yes     Pathogenic
c.148G>A p.Val50Met missense Yes - - -     Likely
pathogenic
c.148G>C p.Val50Leu missense - Yes - -     Likely
pathogenic
c.150del p.Thr51Profs*56 frameshift - - - - * Pathogenic
c.160C>T p.Arg54Cys missense Yes - Yes Yes     Pathogenic
c.185_195del p.Asp62Valfs*12 frameshift Yes - - - * Pathogenic
c.190C>T p.Gln64* nonsense Yes - - -     Pathogenic
c.207del p.Asp70Thrfs*37 frameshift Yes - Yes Yes * Pathogenic
c.208G>T p.Asp70Tyr missense Yes - - Yes     Pathogenic
c.209A>T p.Asp70Val missense - - - -     Likely
pathogenic
c.214A>C p.Thr72Pro missense Yes - - -     Likely
pathogenic
c.217T>C p.Cys73Arg missense Yes - - Yes     Pathogenic
c.218G>A p.Cys73Tyr missense Yes - - - * Likely
pathogenic
c.265C>A p.Pro89Thr missense Yes - Yes -     Likely
pathogenic
c.272C>T p.Ala91Val missense Yes Yes Yes Yes     Uncertain
significance
c.283T>C p.Trp95Arg missense Yes - - Yes * Pathogenic
c.284G>A p.Trp95* nonsense Yes - - -     Pathogenic
c.285G>T p.Trp95Cys missense Yes - - Yes     Pathogenic
c.305G>T p.Cys102Phe missense - Yes Yes -     Likely
pathogenic
c.350_356delinsATGC p.Val117Aspfs*439 frameshift Yes - - Yes * Pathogenic
c.355C>T p.Arg119Trp missense Yes - Yes Yes     Pathogenic
c.382G>T p.Asp128Tyr missense Yes - - Yes     Pathogenic
c.386G>C p.Trp129Ser missense Yes Yes Yes -     Likely
pathogenic
c.394G>A p.Gly132Arg missense Yes - Yes Yes     Pathogenic
c.443C>A p.Ala148Asp missense Yes - - Yes     Pathogenic
c.445G>A p.Gly149Ser missense Yes - - Yes     Likely
pathogenic
c.445G>C p.Gly149Arg missense Yes - Yes Yes     Pathogenic
c.449C>A p.Ser150* nonsense Yes - - Yes     Pathogenic
c.452A>T p.His151Leu missense Yes - - -     Likely
pathogenic
c.469T>G p.Phe157Val missense Yes - - Yes     Pathogenic
c.490C>T p.Gln164* nonsense Yes - - Yes     Pathogenic
c.503G>A p.Ser168Asn missense - - - - * Uncertain
significance
c.508A>C p.Ser170Arg missense Yes - - Yes     Pathogenic
c.512C>A p.Thr171Asn missense Yes - - Yes     Likely
pathogenic
c.528_529delinsAA p.Cys176* nonsense Yes - Yes Yes * Pathogenic
c.548T>G p.Val183Gly missense Yes - - Yes     Pathogenic
c.563C>T p.Pro188Leu missense Yes - - Yes     Likely
pathogenic
c.577T>C p.Phe193Leu missense Yes - - Yes     Pathogenic
c.590T>G p.Leu197Arg missense Yes - - Yes     Pathogenic
c.601C>A p.Pro201Thr missense Yes - Yes Yes     Pathogenic
c.614A>G p.Asn205Ser missense Yes - - Yes     Pathogenic
c.626A>C p.Gln209Pro missense Yes - - Yes     Likely
pathogenic
c.632C>T p.Ala211Val missense - Yes Yes -     Likely
benign
c.643C>A p.Leu215Ile missense Yes - - Yes     Pathogenic
c.655T>A p.Tyr219Asn missense - Yes - Yes     Likely
pathogenic
c.657C>A p.Tyr219* nonsense Yes - - -     Pathogenic
c.658G>A p.Gly220Ser missense Yes - Yes Yes     Pathogenic
c.658G>C p.Gly220Arg missense Yes - - Yes     Pathogenic
c.659G>A p.Gly220Asp missense Yes - - -     Pathogenic
c.662C>T p.Thr221Ile missense Yes - - Yes     Pathogenic
c.665A>G p.His222Arg missense Yes Yes Yes Yes     Pathogenic
c.666C>A p.His222Gln missense Yes - Yes Yes     Pathogenic
c.671T>A p.Ile224Asn missense Yes - Yes -     Likely
pathogenic
c.673C>T p.Arg225Trp missense Yes - Yes Yes     Pathogenic
c.674G>C p.Arg225Pro missense Yes - Yes Yes     Pathogenic
c.694C>T p.Arg232Cys missense Yes - - Yes     Pathogenic
c.695G>A p.Arg232His missense Yes - - Yes     Uncertain
significance
c.718C>G p.Arg240Gly missense Yes - - -     Likely
pathogenic
c.727G>T p.Glu243* nonsense Yes - - Yes     Pathogenic
c.755A>G p.Asn252Ser missense Yes Yes Yes Yes     Uncertain
significance
c.757G>A p.Glu253Lys missense Yes - Yes Yes     Likely
pathogenic
c.781G>A p.Glu261Lys missense Yes - - Yes     Pathogenic
c.785C>A p.Ala262Asp missense Yes - - Yes     Pathogenic
c.785C>T p.Ala262Val missense Yes - - Yes     Pathogenic
c.786_801del p.Gln263Serfs*21 frameshift Yes - - - * Pathogenic
c.797T>C p.Ile266Thr missense Yes - - Yes     Likely
pathogenic
c.833C>A p.Ala278Asp missense - Yes - Yes     Likely
pathogenic
c.836G>A p.Cys279Tyr missense Yes - - Yes     Pathogenic
c.851_862del p.Lys284_Lys287del in-frame
deletion
Yes - - Yes * Likely
pathogenic
c.853_855del p.Lys285del in-frame
deletion
Yes - Yes Yes * Likely
pathogenic
c.879del p.Gln294Lysfs*36 frameshift Yes - - - * Pathogenic
c.886T>C p.Tyr296His missense Yes - Yes Yes     Pathogenic
c.893A>G p.Glu298Gly missense Yes - - Yes     Pathogenic
c.895C>A p.Arg299Ser missense Yes - - Yes     Pathogenic
c.895C>T p.Arg299Cys missense Yes - - -     Likely
pathogenic
c.902C>A p.Ser301* nonsense Yes - - -     Pathogenic
c.916G>A p.Gly306Ser missense Yes - Yes Yes     Likely
pathogenic
c.916G>T p.Gly306Cys missense Yes - Yes Yes     Pathogenic
c.938A>T p.Asp313Val missense Yes - - -     Likely
pathogenic
c.941_948delinsA p.Leu314Glnfs*14 frameshift Yes - - Yes * Pathogenic
c.949G>A p.Gly317Arg missense Yes - - -     Likely
pathogenic
c.992C>T p.Ser331Leu missense - Yes - Yes     Likely
pathogenic
c.1000G>A p.Gly334Ser missense - - - -     Uncertain
significance
c.1018G>A p.Asp340Asn missense Yes - - Yes     Pathogenic
c.1034C>G p.Pro345Arg missense Yes - - -     Likely
pathogenic
c.1034C>T p.Pro345Leu missense Yes - - -     Likely
pathogenic
c.1042G>A p.Val348Met missense Yes Yes Yes -     Uncertain
significance
c.1066C>T p.Arg356Trp missense Yes - - Yes     Pathogenic
c.1081A>T p.Arg361Trp missense Yes - - Yes     Pathogenic
c.1083del p.Arg362Glyfs*3 frameshift Yes - - - * Pathogenic
c.1090_1091del p.Leu364Glufs*93 frameshift Yes - Yes - * Pathogenic
c.1091T>G p.Leu364Arg missense Yes - - Yes     Pathogenic
c.1099T>C p.Tyr367His missense Yes - - Yes     Pathogenic
c.1120T>G p.Trp374Gly missense Yes - - -     Likely
pathogenic
c.1122G>A p.Trp374* nonsense Yes - Yes Yes     Pathogenic
c.1122G>T p.Trp374Cys missense Yes - - -     Likely
pathogenic
c.1146_1168del p.Pro383Argfs*67 frameshift - - - - * Likely
pathogenic
c.1168C>T p.Arg390* nonsense - Yes - -     Pathogenic
c.1177T>C p.Cys393Arg missense Yes - - -     Likely
pathogenic
c.1179C>A p.Cys393* nonsense Yes - - -     Pathogenic
c.1181_1182insT p.Gln394Hisfs*64 frameshift Yes - - Yes * Pathogenic
c.1183T>C p.Cys395Arg missense Yes - - Yes     Pathogenic
c.1189_1190dup p.His398Alafs*23 frameshift Yes - Yes Yes * Pathogenic
c.1220G>A p.Cys407Tyr missense Yes - - Yes     Likely
pathogenic
c.1226C>A p.Pro409His missense Yes - - Yes     Likely
pathogenic
c.1228C>T p.Arg410Trp missense Yes - - Yes     Likely
pathogenic
c.1229G>A p.Arg410Gln missense - Yes - Yes     Uncertain
significance
c.1243G>A p.Ala415Thr missense Yes - - Yes     Likely
pathogenic
c.1246C>T p.Gln416* nonsense Yes - - Yes     Pathogenic
c.1283G>A p.Trp428* nonsense - - - -     Pathogenic
c.1284G>A p.Trp428* nonsense - - - -     Pathogenic
c.1284G>C p.Trp428Cys missense Yes - - -     Uncertain
significance
c.1286G>A p.Gly429Glu missense Yes - - Yes     Likely
pathogenic
c.1288dup p.Asp430Glyfs*28 frameshift Yes - Yes Yes     Pathogenic
c.1288G>A p.Asp430Asn missense Yes - - Yes     Likely
pathogenic
c.1288G>T p.Asp430Tyr missense Yes - Yes Yes     Likely
pathogenic
c.1297A>C p.Thr433Pro missense - - - -     Uncertain
significance
c.1304C>T p.Thr435Met missense Yes - Yes Yes     Pathogenic
c.1310C>T p.Ala437Val missense - Yes - Yes     Uncertain
significance
c.1313A>G p.Tyr438Cys missense - - - -     Uncertain
significance
c.1314T>A p.Tyr438* nonsense Yes - - -     Pathogenic
c.1337A>C p.Gln446Pro missense Yes - Yes Yes     Likely
pathogenic
c.1337A>G p.Gln446Arg missense - - - -     Uncertain
significance
c.1349C>T p.Thr450Met missense Yes Yes Yes Yes     Pathogenic
c.1361G>A p.Trp454* nonsense - - - -     Pathogenic
c.1376C>T p.Pro459Leu missense Yes - Yes Yes     Uncertain
significance
c.1385C>A p.Ser462* nonsense Yes - - Yes     Pathogenic
c.1423del p.Leu478* nonsense Yes - - - * Pathogenic
c.1433T>G p.Leu478Arg missense Yes - - -     Likely
pathogenic
c.1442A>C p.Gln481Pro missense Yes Yes Yes Yes     Pathogenic
c.1450G>A p.Asp484Asn missense Yes - - - * Likely
pathogenic
c.1450G>T p.Asp484Tyr missense Yes - - -     Likely
pathogenic
c.1451del p.Asp484Valfs*25 frameshift Yes - - Yes * Pathogenic
c.1465A>T p.Arg489Trp missense - Yes - -     Uncertain
significance
c.1471G>A p.Asp491Asn missense Yes Yes Yes Yes     Likely
pathogenic
c.1491T>A p.Cys497* nonsense Yes - - -     Pathogenic
c.1535T>G p.Leu512Arg missense Yes - - - * Uncertain
significance
c.1568C>A p.Ala523Asp missense Yes - - -     Uncertain
significance
c.1574G>C p.Cys525Ser missense - - - -     Uncertain
significance
c.1577del p.Leu526Cysfs*87 frameshift Yes - - - * Likely
pathogenic
c.1628dup p.Glu545Glyfs*41 frameshift Yes - - Yes * Pathogenic
c.1637del p.Pro546Leufs*67 frameshift Yes - - Yes * Pathogenic

aThe coding DNA reference sequence of genetic variants (c.) is the CDS of ENST00000441259.2, which is equivalent to that of NM_001083116.3.
bThe protein reference sequence used of protein variants (p.) is ENSP00000398568.1, which is equivalent to NP_001076585.1.
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 PRF1 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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