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Many genetic precision treatments are currently in development for SYNGAP1.
Which treatments target which variant classes?
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Summary of #s likely to be amenable to each strategy
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type of treatment:up-regulate both allelesbase editprime edittRNA suppressor
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% variants likely to be amenable to the treatment79%38%94%30%
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amenable/total64/8131/8176/8124/81
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List of Syngap1 variants from first 81 patients in Ciitizen, ordered by cDNA position;
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showing classification, and which treatments in development likely to be amenable
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cDNA# (or near)VariantProteinClassificationVUS?up-regulate both allelesbase editprime edittRNA suppressor
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28c.28C>Tp.R10WMissenseVUSA>G revprime
Summary (excl VUS) - n=76
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190c.190-2A>GIntronic+C>T revprimeFrameshift3039.47%
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250c.250C>Gp.R84GMissenseVUSprimeGene Deletion22.63%
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333c.333delp.K114Sfs*20Frameshift+prime
Gene Duplication
11.32%
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333c.333delAp.K114Sfs*20Frameshift+prime
Intragenic Deletion
22.63%
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388c.388-3C>GIntronic+primeIntronic79.21%
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403c.403C>Tp.R135XNonsense+A>G revprime
Arg CGA (TGA)
Missense1013.16%
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403c.403C>Tp.R135XNonsense+A>G revprime
Arg CGA (TGA)
Nonsense2431.58%
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490c.490C>Tp.R164XNonsense+A>G revprime
Arg CGA (TGA)
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490c.490C>Tp.R164XNonsense+A>G revprime
Arg CGA (TGA)
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490c.490C>Tp.R164XNonsense+A>G revprime
Arg CGA (TGA)
Recurrent Variants
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490c.490C>Tp.R164XNonsense+A>G revprime
Arg CGA (TGA)
p.R164X5
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490c.490C>Tp.R164XNonsense+A>G revprime
Arg CGA (TGA)
p.R621X3
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535c.535delGp.E179Sfs*9Frameshift+primep.G391Afs*122
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654c.654_655delp.F218Lfs*3Frameshift+primep.G391Qfs*272
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673c.673delTp.S225Hfs*26Frameshift+primep.K114Sfs*202
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698c.698_699dupGTp.R234Vfs*18Frameshift+primep.Q1093X2
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745c.745delp.A249Qfs*2Frameshift+primep.R1240X2
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762c.762+1G>TIntronic+primep.R135X2
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768c.768_770delCAGinsAAp.N256Kfs*5Frameshift+primec.3583-9G>A2
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781c.781_784delGACAp.D261Mfs*3Frameshift+prime
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828c.828dupp.K277Qfs*7Frameshift+prime
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878c.878delGp.R293Pfs*54Frameshift+prime
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949c.949delCp.L317Cfs*30Frameshift+prime
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980c.980T>Cp.L327PMissenseC>Tprime
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1022c.1022_1030delinsTAp.G341Vfs*4Frameshift+prime
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1030c.1030G>Ap.G344SMissenseA>Gprime
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1154c.1154_1161delp.S385fsFrameshift+prime
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1167c.1167_1168delAGp.G391Qfs*27Frameshift+prime
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1167c.1167_1168delp.G391Qfs*27Frameshift+prime
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1167c.1167_1168delp.G391fsFrameshift+prime
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1167c.1167delAp.G391Afs*12Frameshift+prime
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1284c.1284T>Ap.Y428XNonsense+primeTyr TAT (TAA)
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1292c.1292T>Cp.L431PMissenseC>Tprime
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1329c.1329_1333delCAAGGp.K444Gfs*27Frameshift+prime
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1403c.1403T>Ap.M468KMissenseprime
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1463c.1463delCp.T488fsFrameshift+prime
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1507c.1507C>Tp.Q503XNonsense+A>G revprimeGln CAG (TAG)
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1715c.1715G>Cp.W572SMissenseprime
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1735c.1735C>Tp.R579XNonsense+A>G revprimeArg CGA (TGA)
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1744c.1744delp.E582Rfs*68Frameshift+prime
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1797c.1797C>Gp.C599WMissenseprime
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1861c.1861C>Tp.R621XNonsense+A>G revprimeArg CGA (TGA)
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1861c.1861C>Tp.R621XNonsense+A>G revprimeArg CGA (TGA)
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1861c.1861C>Tp.R621XNonsense+A>G revprimeArg CGA (TGA)
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1889c.1889T>Ap.I630NMissenseprime
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1898c.1898T>Cp.L633PMissenseC>Tprime
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1913c.1913+1G>AIntronic+A>Gprime
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1946c.1946T>Gp.M649RMissenseprime
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2059c.2059C>Tp.R687XNonsense+A>G revprimeArg CGA (TGA)
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2104c.2104C>Tp.Q702XNonsense+A>G revprimeGln CAG (TAG)
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2293c.2293delAp.S765Afs*44Frameshift+prime
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2438c.2438delTp.L813Rfs*23Frameshift+prime
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2523c.2523_2524delp.S842Hfs*7Frameshift+prime
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2886c.2886_2888dupp.H966dupIntragenic DuplicationVUSprime
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2916c.2916delTp.D974Tfs*103Frameshift+prime
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2946c.2946T>Ap.Y982XNonsense+primeTyr TAT (TAA)
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3124c.3124C>Tp.Q1042XNonsense+A>G revprimeGln CAG (TAG)
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3190c.3190C>Tp.Q1064XNonsense+A>G revprimeGln CAG (TAG)
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3227c.3227delTp.L1076XFrameshift+prime
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3233c.3233_3236delp.V1078Afs*51Frameshift+prime
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3277c.3277C>Tp.Q1093XNonsense+A>G revprimeGln CAG (TAG)
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3277c.3277C>Tp.Q1093XNonsense+A>G revprimeGln CAG (TAG)
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3316c.3316C>Tp.Q1106XNonsense+A>G revprimeGln CAG (TAG)
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3348c.3384dupp.L1129Afs*24Frameshift+prime
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3380c.3380G>Cp.G1127AMissenseVUSprime
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3416c.3416dupAp.T1140Dfs*13Frameshift+prime
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3553c.3553A>Tp.K1185XNonsense+primeLys AAA (TAA)
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3583c.3583-9G>Ap.V1195Afs*27Intronic+A>Gprime
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3583c.3583-9G>Ap.V1195Afs*27Intronic+A>Gprime
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3653c.3653A>Tp.E1218VMissenseVUSprime
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3665c.3665_3669dupGGCTGp.L1224Gfs*13Frameshift+prime
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3718c.3718C>Tp.R1240XNonsense+A>G revprimeArg CGA (TGA)
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3718c.3718C>Tp.R1240XNonsense+A>G revprimeArg CGA (TGA)
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3795c.3795-1G>CIntronic+prime
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4006c.4006G>Ap.E1336KMissenseA>Gprime
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del ex3
Intragenic Deletion
+
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del ex4-5
Intragenic Deletion
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DuplicationGene Duplication
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chr16:33,451,137-33,543,925x1Gene Deletion+
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DeletionGene Deletion+
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Notes:
1. table made from a summary list from Ciitizen; some information incomplete (size of deletion, exact boundaries of deletions and duplication)
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2. intronic predicted protein listed when RNAseq reported
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3. table made by JR, to help the entire community; may contain errors.
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4. will be updated with each release of data from Ciitizen.
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5. send updates to treatments in development to mike@syngapresearchfund.org