TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17307	52144;52145;52146	chr2:178609391;178609390;178609389	chr2:179474118;179474117;179474116
N2AB	15666	47221;47222;47223	chr2:178609391;178609390;178609389	chr2:179474118;179474117;179474116
N2A	14739	44440;44441;44442	chr2:178609391;178609390;178609389	chr2:179474118;179474117;179474116
N2B	8242	24949;24950;24951	chr2:178609391;178609390;178609389	chr2:179474118;179474117;179474116
Novex-1	8367	25324;25325;25326	chr2:178609391;178609390;178609389	chr2:179474118;179474117;179474116
Novex-2	8434	25525;25526;25527	chr2:178609391;178609390;178609389	chr2:179474118;179474117;179474116
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-112
• Domain position: 57
• Structural Position: 89
• Q(SASA): 0.1857
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/A	rs745810412	-1.006	0.704	N	0.411	0.148	0.354610295913	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/A	rs745810412	-1.006	0.704	N	0.411	0.148	0.354610295913	gnomAD-4.0.0	1.59449E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86366E-06	0	0
E/K	None	None	0.704	N	0.441	0.189	0.306377322295	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.104	likely_benign	0.1036	benign	0.03	Stabilizing	0.704	D	0.411	neutral	N	0.494959729	None	None	N
E/C	0.6127	likely_pathogenic	0.6225	pathogenic	-0.286	Destabilizing	0.999	D	0.478	neutral	None	None	None	None	N
E/D	0.0809	likely_benign	0.0857	benign	-0.452	Destabilizing	0.959	D	0.419	neutral	N	0.495133087	None	None	N
E/F	0.4279	ambiguous	0.4128	ambiguous	-0.065	Destabilizing	0.997	D	0.44	neutral	None	None	None	None	N
E/G	0.1223	likely_benign	0.123	benign	-0.056	Destabilizing	0.015	N	0.221	neutral	N	0.495826521	None	None	N
E/H	0.2665	likely_benign	0.2588	benign	0.582	Stabilizing	0.997	D	0.414	neutral	None	None	None	None	N
E/I	0.1688	likely_benign	0.1652	benign	0.196	Stabilizing	0.997	D	0.449	neutral	None	None	None	None	N
E/K	0.1214	likely_benign	0.117	benign	0.339	Stabilizing	0.704	D	0.441	neutral	N	0.456652057	None	None	N
E/L	0.2182	likely_benign	0.2195	benign	0.196	Stabilizing	0.969	D	0.425	neutral	None	None	None	None	N
E/M	0.2532	likely_benign	0.2577	benign	-0.08	Destabilizing	0.999	D	0.413	neutral	None	None	None	None	N
E/N	0.1453	likely_benign	0.1499	benign	0.124	Stabilizing	0.969	D	0.418	neutral	None	None	None	None	N
E/P	0.2752	likely_benign	0.2652	benign	0.157	Stabilizing	0.997	D	0.393	neutral	None	None	None	None	N
E/Q	0.1206	likely_benign	0.1239	benign	0.118	Stabilizing	0.92	D	0.445	neutral	N	0.494959729	None	None	N
E/R	0.1943	likely_benign	0.1801	benign	0.55	Stabilizing	0.046	N	0.187	neutral	None	None	None	None	N
E/S	0.134	likely_benign	0.1361	benign	0.003	Stabilizing	0.939	D	0.398	neutral	None	None	None	None	N
E/T	0.1265	likely_benign	0.1245	benign	0.083	Stabilizing	0.969	D	0.396	neutral	None	None	None	None	N
E/V	0.1204	likely_benign	0.1185	benign	0.157	Stabilizing	0.988	D	0.417	neutral	N	0.45838564	None	None	N
E/W	0.6993	likely_pathogenic	0.689	pathogenic	-0.053	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	N
E/Y	0.3619	ambiguous	0.3525	ambiguous	0.145	Stabilizing	0.997	D	0.412	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.