TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31893	95902;95903;95904	chr2:178545433;178545432;178545431	chr2:179410160;179410159;179410158
N2AB	30252	90979;90980;90981	chr2:178545433;178545432;178545431	chr2:179410160;179410159;179410158
N2A	29325	88198;88199;88200	chr2:178545433;178545432;178545431	chr2:179410160;179410159;179410158
N2B	22828	68707;68708;68709	chr2:178545433;178545432;178545431	chr2:179410160;179410159;179410158
Novex-1	22953	69082;69083;69084	chr2:178545433;178545432;178545431	chr2:179410160;179410159;179410158
Novex-2	23020	69283;69284;69285	chr2:178545433;178545432;178545431	chr2:179410160;179410159;179410158
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-120
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.4527
• Predicted PPI site: I

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/K	rs1241275942	0.531	0.704	N	0.484	0.222	0.353974658523	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.02E-06	0
E/K	rs1241275942	0.531	0.704	N	0.484	0.222	0.353974658523	gnomAD-4.0.0	3.23073E-06	None	None	None	None	I	None	0	0	None	0	2.78987E-05	None	0	0	2.91688E-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	0.1176	likely_benign	0.11	benign	-0.37	Destabilizing	0.134	N	0.24	neutral	N	0.497143524	None	None	I
E/C	0.7503	likely_pathogenic	0.7271	pathogenic	-0.016	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	I
E/D	0.1289	likely_benign	0.1231	benign	-0.305	Destabilizing	0.826	D	0.471	neutral	D	0.523964766	None	None	I
E/F	0.608	likely_pathogenic	0.568	pathogenic	-0.288	Destabilizing	0.997	D	0.614	neutral	None	None	None	None	I
E/G	0.1762	likely_benign	0.1625	benign	-0.555	Destabilizing	0.852	D	0.557	neutral	N	0.482547279	None	None	I
E/H	0.422	ambiguous	0.3885	ambiguous	-0.029	Destabilizing	0.991	D	0.561	neutral	None	None	None	None	I
E/I	0.1992	likely_benign	0.1778	benign	0.079	Stabilizing	0.991	D	0.619	neutral	None	None	None	None	I
E/K	0.1141	likely_benign	0.0993	benign	0.34	Stabilizing	0.704	D	0.484	neutral	N	0.508360596	None	None	I
E/L	0.2098	likely_benign	0.1933	benign	0.079	Stabilizing	0.939	D	0.625	neutral	None	None	None	None	I
E/M	0.2891	likely_benign	0.2595	benign	0.183	Stabilizing	0.997	D	0.621	neutral	None	None	None	None	I
E/N	0.2306	likely_benign	0.2083	benign	0.046	Stabilizing	0.969	D	0.597	neutral	None	None	None	None	I
E/P	0.2912	likely_benign	0.2844	benign	-0.051	Destabilizing	0.046	N	0.321	neutral	None	None	None	None	I
E/Q	0.1132	likely_benign	0.1054	benign	0.075	Stabilizing	0.31	N	0.124	neutral	N	0.491390988	None	None	I
E/R	0.2143	likely_benign	0.1948	benign	0.531	Stabilizing	0.939	D	0.595	neutral	None	None	None	None	I
E/S	0.171	likely_benign	0.1597	benign	-0.117	Destabilizing	0.759	D	0.471	neutral	None	None	None	None	I
E/T	0.1841	likely_benign	0.169	benign	0.035	Stabilizing	0.939	D	0.571	neutral	None	None	None	None	I
E/V	0.1317	likely_benign	0.1208	benign	-0.051	Destabilizing	0.92	D	0.615	neutral	N	0.483258522	None	None	I
E/W	0.8608	likely_pathogenic	0.8375	pathogenic	-0.148	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
E/Y	0.4927	ambiguous	0.4542	ambiguous	-0.047	Destabilizing	0.997	D	0.623	neutral	None	None	None	None	I

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.