TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33183	99772;99773;99774	chr2:178537660;178537659;178537658	chr2:179402387;179402386;179402385
N2AB	31542	94849;94850;94851	chr2:178537660;178537659;178537658	chr2:179402387;179402386;179402385
N2A	30615	92068;92069;92070	chr2:178537660;178537659;178537658	chr2:179402387;179402386;179402385
N2B	24118	72577;72578;72579	chr2:178537660;178537659;178537658	chr2:179402387;179402386;179402385
Novex-1	24243	72952;72953;72954	chr2:178537660;178537659;178537658	chr2:179402387;179402386;179402385
Novex-2	24310	73153;73154;73155	chr2:178537660;178537659;178537658	chr2:179402387;179402386;179402385
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-156
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.229
• 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/D	None	None	0.993	N	0.495	0.288	0.376921832658	gnomAD-4.0.0	1.59128E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.1817	likely_benign	0.195	benign	-0.415	Destabilizing	0.999	D	0.706	prob.neutral	N	0.495611192	None	None	I
E/C	0.8867	likely_pathogenic	0.9108	pathogenic	-0.106	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
E/D	0.3003	likely_benign	0.3611	ambiguous	-0.458	Destabilizing	0.993	D	0.495	neutral	N	0.488218133	None	None	I
E/F	0.8539	likely_pathogenic	0.9046	pathogenic	-0.135	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
E/G	0.2824	likely_benign	0.3325	benign	-0.652	Destabilizing	1.0	D	0.771	deleterious	N	0.52156626	None	None	I
E/H	0.6119	likely_pathogenic	0.63	pathogenic	0.049	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
E/I	0.493	ambiguous	0.6001	pathogenic	0.187	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
E/K	0.1943	likely_benign	0.209	benign	0.307	Stabilizing	1.0	D	0.578	neutral	N	0.485038128	None	None	I
E/L	0.5513	ambiguous	0.6458	pathogenic	0.187	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
E/M	0.5463	ambiguous	0.6284	pathogenic	0.266	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
E/N	0.4374	ambiguous	0.4832	ambiguous	-0.152	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/P	0.9201	likely_pathogenic	0.954	pathogenic	0.007	Stabilizing	0.999	D	0.815	deleterious	None	None	None	None	I
E/Q	0.1482	likely_benign	0.1431	benign	-0.091	Destabilizing	1.0	D	0.641	neutral	D	0.535523846	None	None	I
E/R	0.349	ambiguous	0.3675	ambiguous	0.551	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
E/S	0.242	likely_benign	0.2403	benign	-0.307	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
E/T	0.2329	likely_benign	0.2544	benign	-0.108	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
E/V	0.281	likely_benign	0.3543	ambiguous	0.007	Stabilizing	1.0	D	0.813	deleterious	N	0.489636938	None	None	I
E/W	0.9554	likely_pathogenic	0.9721	pathogenic	0.07	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
E/Y	0.8031	likely_pathogenic	0.8621	pathogenic	0.129	Stabilizing	1.0	D	0.814	deleterious	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.