TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19197	57814;57815;57816	chr2:178595765;178595764;178595763	chr2:179460492;179460491;179460490
N2AB	17556	52891;52892;52893	chr2:178595765;178595764;178595763	chr2:179460492;179460491;179460490
N2A	16629	50110;50111;50112	chr2:178595765;178595764;178595763	chr2:179460492;179460491;179460490
N2B	10132	30619;30620;30621	chr2:178595765;178595764;178595763	chr2:179460492;179460491;179460490
Novex-1	10257	30994;30995;30996	chr2:178595765;178595764;178595763	chr2:179460492;179460491;179460490
Novex-2	10324	31195;31196;31197	chr2:178595765;178595764;178595763	chr2:179460492;179460491;179460490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-27
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.3047
• 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
T/I	None	None	1.0	N	0.808	0.461	0.45470266194	gnomAD-4.0.0	6.86581E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01203E-07	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
T/A	0.2436	likely_benign	0.2919	benign	-0.86	Destabilizing	0.999	D	0.537	neutral	N	0.472817724	None	None	N
T/C	0.6791	likely_pathogenic	0.6633	pathogenic	-0.654	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
T/D	0.4498	ambiguous	0.554	ambiguous	-0.797	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
T/E	0.6003	likely_pathogenic	0.706	pathogenic	-0.781	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
T/F	0.6678	likely_pathogenic	0.7579	pathogenic	-0.892	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/G	0.3045	likely_benign	0.3615	ambiguous	-1.131	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
T/H	0.4803	ambiguous	0.5303	ambiguous	-1.418	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/I	0.6494	likely_pathogenic	0.7245	pathogenic	-0.22	Destabilizing	1.0	D	0.808	deleterious	N	0.492024843	None	None	N
T/K	0.4697	ambiguous	0.5599	ambiguous	-0.862	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
T/L	0.3045	likely_benign	0.3711	ambiguous	-0.22	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
T/M	0.2368	likely_benign	0.2826	benign	0.119	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
T/N	0.1435	likely_benign	0.1648	benign	-0.926	Destabilizing	1.0	D	0.794	deleterious	N	0.51719351	None	None	N
T/P	0.6443	likely_pathogenic	0.7744	pathogenic	-0.401	Destabilizing	1.0	D	0.788	deleterious	N	0.507166583	None	None	N
T/Q	0.3996	ambiguous	0.4707	ambiguous	-1.127	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/R	0.4278	ambiguous	0.5174	ambiguous	-0.586	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/S	0.1209	likely_benign	0.1334	benign	-1.15	Destabilizing	0.999	D	0.569	neutral	N	0.465956613	None	None	N
T/V	0.4997	ambiguous	0.548	ambiguous	-0.401	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
T/W	0.8708	likely_pathogenic	0.9076	pathogenic	-0.836	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/Y	0.6778	likely_pathogenic	0.7379	pathogenic	-0.588	Destabilizing	1.0	D	0.777	deleterious	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.