Review Article
Hints for Genetic and Clinical Differentiation of Adult-Onset Monogenic Autoinflammatory Diseases
Table 7
Genetic variants associated with hereditary recurrent febrile syndromes and interpretations of their significance (from ClinVar database).
| | Disease | Gene—locus (NM) | Location | Sequence variant (protein variant) | SNP no. | Clinical significance |
| | Familial Mediterranean fever (FMF, #249100) | MEFV—16p13.3 (NM_000243.2) | Exon 1 | c.97G>T (p.Val33Leu) | rs11466016 | US | | Exon 2 | c.289C>T (p.Gln97Ter) | rs138498376 | US | | Exon 2 | c.277G>C (p.Glu93Gln) | rs747515115 | US | | Exon 2 | c.329T>C (p.Leu110Pro) | rs11466018 | US | | Exon 2 | c.343C>A (p.Pro115Thr) | rs147557169 | US | | Exon 2 | c.442G>C (p.Glu148Gln) | rs3743930 | P/US/LB | | Exon 2 | c.443A>T (p.Glu148Val) | rs104895076 | P/US | | Exon 2 | c.501G>C (p.Glu167Asp) | rs104895079 | P | | Exon 2 | c.605G>A (p.Arg202Gln) | rs224222 | LB/B | | Exon 2 | c.611G>A (p.Arg204His) | rs775663363 | US | | Exon 2 | c.688G>A (p.Glu230Lys) | rs104895080 | US | | Exon 2 | c.800C>T (p.Thr267Ile) | rs104895081 | P | | Exon 2 | c.910G>A (p.Gly304Arg) | rs75977701 | US/LB | | Exon 3 | c.941G>A (p.Arg314His) | rs104895204 | US | | Exon 3 | c.986G>A (p.Arg329His) | rs104895112 | US | | Exon 3 | c.1016C>T (p.Ser339Phe) | rs104895157 | US | | Exon 3 | c.1043G>A (p.Arg348His) | rs104895198 | US | | Exon 3 | c.1105C>T (p.Pro369Ser) | rs11466023 | P/LP/US | | Exon 3 | c.1222C>T (p.Arg408Trp) | rs758868622 | US | | Exon 3 | c.1223G>A (p.Arg408Gln) | rs11466024 | P/US/B | | Exon 3 | c.1223G>T (p.Arg408Leu) | rs11466024 | US | | Exon 3 | c.1318C>G (p.Gln440Glu) | rs11466026 | US/B | | Exon 5 | c.1370C>T (p.Ala457Val) | rs104895151 | US | | Exon 5 | c.1406T>C (p.Val469Ala) | rs778686119 | US | | Exon 5 | c.1437C>G (p.Phe479Leu) | rs104895083 | P | | Exon 5 | c.1459G>C (p.Val487Leu) | rs104895100 | LB | | Exon 5 | c.1508C>G (p.Ser503Cys) | rs190705322 | US | | Exon 5 | c.1513G>T (p.Asp505Tyr) | rs150730718 | US | | Exon 8 | c.1730C>A (p.Thr577Asn) | rs1057516210 | P | | Exon 8 | c.1736G>A (p.Arg579His) | rs574055513 | US | | Exon 9 | c.1772T>C (p.Ile591Thr) | rs11466045 | P/US/LB | | Exon 10 | c.1894G>A (p.Gly632Ser) | rs104895128 | LP | | Exon 10 | c.1898C>T (p.Pro633Leu) | rs976279218 | US | | Exon 10 | c.1958G>A (p.Arg653His) | rs104895085 | P | | Exon 10 | c.2040G>A (p.Met680Ile) | rs28940580 | P | | Exon 10 | c.2040G>C (p.Met680Ile) | rs28940580 | P | | Exon 10 | c.2064C>G (p.Tyr688Ter) | rs104895098 | P | | Exon 10 | c.2076_2078delAAT (p.Ile692del) | rs104895093 | P | | Exon 10 | c.2080A>G (p.Met694Val) | rs61752717 | P | | Exon 10 | c.2081_2083delTGA (p.Met694del) | rs104895091 | P | | Exon 10 | c.2082G>A (p.Met694Ile) | rs28940578 | P | | Exon 10 | c.2084A>G (p.Lys695Arg) | rs104895094 | P/LP/LB | | Exon 10 | c.2177T>C (p.Val726Ala) | rs28940579 | P | | Exon 10 | c.2230G>T (p.Ala744Ser) | rs61732874 | P/LP | | Exon 10 | c.2282G>A (p.Arg761His) | rs104895097 | P/LP | | Exon 10 | c.2330_2331del (p.(Gly777Alafs4)) | rs753946287 | US |
| | Hyperimmunoglobulinemia D syndrome (HIDS, #610377) | MVK—12q24 (NM_052845.3) | Exon 2 | c.16_34del (p.(Leu6Glyfs16)) | rs104895334 | P | | Exon 2 | c.56G>A (p.Arg19His) | rs10774775 | B | | Exon 2 | c.59A>C (p.His20Pro) | rs104895295 | P | | Exon 3 | c.72dup (p.(Gly25Trpfs55)) | rs104895322 | P | | Exon 3 | c.155G>A (p.Ser52Asn) | rs7957619 | LB/B | | Exon 4 | c.238G>A (p.Val80Ile) | rs76914224 | US/LB | | Exon 4 | c.302G>A (p.Cys101Tyr) | rs886048931 | US | | Exon 4 | c.317G>A (p.Arg106His) | rs778337320 | US | | Exon 4 | c.331G>A (p.Ala111Thr) | rs371257609 | US | | Exon 4 | c.346T>C (p.Tyr116His) | rs104895382 | P | | Exon 5 | c.417dup (p.(Gly140Argfs47)) | rs104895373 | P | | Exon 5 | c.421dup (p.(Ala141Glyfs46)) | rs104895323 | P | | Exon 5 | c.442G>A (p.Ala148Thr) | rs104895298 | P | | Exon 5 | c.494C>T (p.Pro165Leu) | rs121917790 | P | | Exon 5 | c.500C>T (p.Pro167Leu) | rs104895300 | P/LP | | Exon 6 | c.564G>A (p.Trp188Ter) | rs104895311 | P | | Exon 6 | c.598C>T (p.Pro200Ser) | rs886048932 | US | | Exon 6 | c.604G>A (p.Gly202Arg) | rs104895301 | P | | Exon 6 | c.608T>C (p.Val203Ala) | rs104895332 | P | | Exon 8 | c.709A>T (p.Thr237Ser) | rs104895366 | P | | Exon 9 | c.803T>C (p.Ile268Thr) | rs104895304 | P | | Exon 9 | c.857C>T (p.Pro286Leu) | rs104895379 | US | | Exon 10 | c.904C>T (p.Gln302Ter) | rs886048933 | LP/US | | Exon 10 | c.928G>A (p.Val310Met) | rs104895319 | P | | Exon 10 | c.1000G>A (p.Ala334Thr) | rs104895317 | P | | Exon 11 | c.1129G>A (p.Val377Ile) | rs28934897 | P | | Exon 11 | c.1156G>A (p.Asp386Asn) | rs104895380 | LB | | Exon 11 | c.1162C>T (p.Arg388Ter) | rs104895360 | P | | Exon 11 | c.1163G>A (p.Arg388Gln) | rs886048934 | US |
| | Tumor necrosis factor-associated periodic syndrome (TRAPS, #142680) | TNFRSF1A—12p13 (NM_001065.3) | Exon 2 | c.92T>G (p.Val31Gly) | rs763940329 | US | | Exon 2 | c.123T>G (p.Asp41Glu) | rs104895271 | LP | | Exon 2 | c.175T>C (p.Cys59Arg) | rs104895217 | P | | Exon 2 | c.176G>C (p.Cys59Ser) | rs104895223 | P | | Exon 2 | c.176G>A (p.Cys59Tyr) | rs104895223 | US | | Exon 2 | c.184T>G (p.Cys62Gly) | rs104895225 | P | | Exon 2 | c.185G>A (p.Cys62Tyr) | rs104895218 | P | | Exon 3 | c.211_213delGAC (p.Asp71del) | rs104895246 | P | | Exon 3 | c.224C>T (p.Pro75Leu) | rs4149637 | LB/B | | Exon 3 | c.236C>T (p.Thr79Met) | rs104895219 | P | | Exon 3 | c.242G>T (p.Cys81Phe) | rs104895220 | P | | Exon 3 | c.265T>C (p.Phe89Leu) | rs104895245 | LP | | Exon 3 | c.282C>G (p.Asn94Lys) | rs876661014 | LP | | Exon 3 | c.287T>C (p.Leu96Pro) | rs104895235 | US | | Exon 3 | c.295T>A (p.Cys99Ser) | rs104895228 | P | | Exon 3 | c.295T>C (p.Cys99Arg) | rs104895228 | P | | Exon 3 | c.305G>C (p.Cys102Ser) | — | LP | | Exon 3 | c.317G>A (p.Arg106Gln) | rs876661031 | LP | | Exon 4 | c.334G>A (p.Val112Met) | rs201753543 | US | | Exon 4 | c.349T>C (p.Cys117Arg) | rs104895221 | P | | Exon 4 | c.350G>A (p.Cys117Tyr) | rs104895222 | P | | Exon 4 | c.362G>A (p.Arg121Gln) | rs4149584 | P/US/LB/B | | Exon 4 | c.362G>C (p.Arg121Pro) | rs4149584 | P | | Exon 4 | c.370G>A (p.Val124Met) | rs104895278 | US | | Exon 4 | c.434A>G (p.Asn145Ser) | rs104895288 | US | | Exon 5 | c.532G>A (p.Glu178Lys) | rs538872981 | US | | Exon 6 | c.596T>C (p.Ile199Thr) | rs104895247 | P/US | | Exon 9 | c.806C>G (p.Pro269Arg) | rs876661237 | US | | Exon 9 | c.823C>T (p.Pro275Ser) | rs758118907 | US | | Exon 9 | c.935G>A (p.Arg312Lys) | — | P/LB/B | | Exon 9 | c.959G>A (p.Gly320Glu) | rs1057524143 | LB | | Exon 9 | c.988G>A (p.Ala330Thr) | rs200029309 | US/LB | | Exon 10 | c.1159C>T (p.Arg387Trp) | — | US | | Exon 10 | c.1234C>G (p.Pro412Ala) | rs876661181 | US | | Exon 10 | c.1328G>T (p.Gly443Val) | rs201062001 | US | | Exon 10 | c.1356T>A (p.Ser452Arg) | rs886049750 | US |
| | Cryopyrin-associated periodic syndrome: familial cold autoinflammatory syndrome (FCAS, #120100), Muckle-Wells syndrome (MWS, #191900), chronic infantile neurological cutaneous articular syndrome (CINCA, #607115) | NLRP3—1q44 (NM_001243133.1) | Exon 1 | c.61G>C (p.Asp21His) | rs200154873 | P | | Exon 1 | c.82C>T (p.His28Tyr) | rs763551829 | US | | Exon 1 | c.152A>G (p.His51Arg) | rs367663649 | US | | Exon 1 | c.178G>A (p.Asp60Asn) | rs1131691891 | US | | Exon 1 | c.200C>G (p.Ala67Gly) | rs763252989 | US | | Exon 1 | c.209T>C (p.Met70Thr) | rs147559626 | LB | | Exon 1 | c.214G>A (p.Val72Met) | rs117287351 | LB | | Exon 1 | c.230C>A (p.Ala77Glu) | rs200288250 | US | | Exon 1 | c.230C>T (p.Ala77Val) | rs200288250 | US | | Exon 2 | c.298C>T (p.Arg100Cys) | rs375013904 | US | | Exon 2 | c.299G>A (p.Arg100His) | rs201887896 | US | | Exon 2 | c.392A>G (p.Lys131Arg) | rs188623199 | US | | Exon 3 | c.410G>A (p.Arg137His) | rs138946894 | US | | Exon 3 | c.494A>G (p.Asn165Ser) | rs199475733 | US/LB | | Exon 3 | c.584C>T (p.Thr195Met) | rs76291085 | US | | Exon 3 | c.592G>A (p.Val198Met) | rs121908147 | P/US/LB/B | | Exon 3 | c.634G>A (p.Asp212Asn) | rs372038150 | US | | Exon 3 | c.644A>G (p.His215Arg) | rs150396172 | US | | Exon 3 | c.674C>T (p.Ala225Val) | rs180177493 | US | | Exon 3 | c.749A>G (p.Gln250Arg) | rs876660971 | US | | Exon 3 | c.766C>A (p.Leu256Met) | — | US | | Exon 3 | c.778C>T (p.Arg260Trp) | rs121908150 | P | | Exon 3 | c.907G>A (p.Asp303Asn) | rs121908153 | P | | Exon 3 | c.910G>A (p.Glu304Lys) | rs180177484 | P | | Exon 3 | c.914T>C (p.Leu305Pro) | rs180177431 | LP | | Exon 3 | c.925G>C (p.Gly309Arg) | rs1057524777 | LP | | Exon 3 | c.926T>C (p.Phe309Ser) | rs121908154 | P | | Exon 3 | c.937A>G (p.Ile313Val) | rs180177501 | US | | Exon 3 | c.944C>T (p.Pro315Leu) | rs180177462 | US/LB | | Exon 3 | c.1027G>A (p.Glu343Lys) | rs369910640 | US | | Exon 3 | c.1043C>T (p.Thr348Met) | rs151344629 | P | | Exon 3 | c.1055C>T (p.Ala352Val) | rs121908149 | P | | Exon 3 | c.1058T>C (p.Leu353Pro) | rs28937896 | P | | Exon 3 | c.1070A>G (p.Lys357Arg) | rs876660972 | US | | Exon 3 | c.1071A>C (p.Lys357Asn) | rs1131691298 | P | | Exon 3 | c.1108A>C (p.Ile370Leu) | rs200735245 | US | | Exon 3 | c.1213A>C (p.Thr405Pro) | rs180177445 | P | | Exon 3 | c.1303A>G (p.Thr435Ala) | rs876661016 | US | | Exon 3 | c.1306A>G (p.Thr436Ala) | rs180177465 | LP | | Exon 3 | c.1316C>T (p.Ala439Val) | rs121908146 | P | | Exon 3 | c.1339C>T (p.Leu447Phe) | rs202121800 | US | | Exon 3 | c.1367G>A (p.Gly456Glu) | rs199696688 | US | | Exon 3 | c.1463G>A (p.Arg488Lys) | rs145268073 | US/LB | | Exon 3 | c.1631C>T (p.Thr544Met) | rs199856287 | US | | Exon 3 | c.1705G>C (p.Gly569Arg) | rs121908151 | P | | Exon 3 | c.1711G>A (p.Gly571Arg) | rs121908151 | P | | Exon 3 | c.1718T>C (p.Phe573Ser) | rs121908152 | P | | Exon 3 | c.1789A>G (p.Ser597Gly) | — | LP | | Exon 3 | c.1805A>G (p.Gln602Arg) | rs1057518827 | LP | | Exon 3 | c.1845A>T (p.Lys615Asn) | rs876660973 | US | | Exon 3 | c.1880A>G (p.Glu627Gly) | rs121908148 | P | | Exon 3 | c.1942G>T (p.Asp648Tyr) | rs138061418 | US | | Exon 3 | c.2113C>A (p.Gln705Lys) | rs35829419 | US | | Exon 3 | c.2113C>A (p.Gln705Lys) | rs35829419 | B | | Exon 3 | c.2138A>T (p.His713Leu) | rs767805817 | LB | | Exon 4 | c.2182A>G (p.Ser728Gly) | rs147946775 | US/LB | | Exon 4 | c.2305G>A (p.Gly769Ser) | rs866534904 | US | | Exon 5 | c.2383A>G (p.Ser795Gly) | rs1064797023 | US | | Exon 5 | c.2398C>A (p.Leu800Met) | rs756392002 | US | | Exon 5 | c.2431G>A (p.Gly811Ser) | rs141389711 | US | | Exon 6 | c.2494C>A (p.Leu832Ile) | rs114158404 | US | | Exon 6 | c.2542G>C (p.Ala848Pro) | rs773376112 | US | | Exon 6 | c.2576A>G (p.Tyr859Cys) | rs180177452 | P | | Exon 6 | c.2617G>A (p.Ala873Thr) | rs201867582 | US | | Exon 6 | c.2638A>G (p.Lys880Glu) | rs1057515488 | US | | Exon 7 | c.2744C>T (p.Thr915Met) | rs765925466 | US | | Exon 7 | c.2759G>A (p.Arg920Gln) | — | P | | Exon 7 | c.2767A>G (p.Thr923Ala) | rs200089542 | US | | Exon 7 | c.2790A>C (p.Lys930Asn) | rs876660975 | US | | Exon 7 | c.2825A>G (p.Lys942Arg) | rs201580005 | US | | Exon 8 | c.2861C>T (p.Thr954Met) | rs139814109 | US/LB | | Exon 8 | c.2895_2902del (p.(Ser966Profs10)) | — | US | | Exon 8 | c.2969G>C (p.Cys990Ser) | rs876660974 | US | | Exon 8 | c.2993G>C (p.Cys998Ser) | rs199517145 | US | | Exon 9 | c.3043A>G (p.Lys1015Glu) | rs771315000 | US |
|
|
List of abbreviations: P: pathogenic; LP: likely pathogenic; US: uncertain significance; LB: likely benign; B: benign.
|
