TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30019	90280;90281;90282	chr2:178552845;178552844;178552843	chr2:179417572;179417571;179417570
N2AB	28378	85357;85358;85359	chr2:178552845;178552844;178552843	chr2:179417572;179417571;179417570
N2A	27451	82576;82577;82578	chr2:178552845;178552844;178552843	chr2:179417572;179417571;179417570
N2B	20954	63085;63086;63087	chr2:178552845;178552844;178552843	chr2:179417572;179417571;179417570
Novex-1	21079	63460;63461;63462	chr2:178552845;178552844;178552843	chr2:179417572;179417571;179417570
Novex-2	21146	63661;63662;63663	chr2:178552845;178552844;178552843	chr2:179417572;179417571;179417570
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-106
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.1233
• 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
C/R	rs774538632	-1.066	0.966	N	0.869	0.336	0.714032942311	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
C/R	rs774538632	-1.066	0.966	N	0.869	0.336	0.714032942311	gnomAD-4.0.0	1.59129E-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
C/A	0.3557	ambiguous	0.289	benign	-1.664	Destabilizing	0.016	N	0.317	neutral	None	None	None	None	I
C/D	0.8548	likely_pathogenic	0.8075	pathogenic	-0.614	Destabilizing	0.974	D	0.863	deleterious	None	None	None	None	I
C/E	0.8463	likely_pathogenic	0.8054	pathogenic	-0.484	Destabilizing	0.949	D	0.865	deleterious	None	None	None	None	I
C/F	0.3214	likely_benign	0.2798	benign	-1.037	Destabilizing	0.989	D	0.776	deleterious	N	0.472121891	None	None	I
C/G	0.2829	likely_benign	0.2366	benign	-1.991	Destabilizing	0.666	D	0.797	deleterious	N	0.475762601	None	None	I
C/H	0.6561	likely_pathogenic	0.5941	pathogenic	-2.125	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	I
C/I	0.5161	ambiguous	0.4657	ambiguous	-0.818	Destabilizing	0.949	D	0.723	deleterious	None	None	None	None	I
C/K	0.8401	likely_pathogenic	0.7925	pathogenic	-0.974	Destabilizing	0.949	D	0.836	deleterious	None	None	None	None	I
C/L	0.5366	ambiguous	0.486	ambiguous	-0.818	Destabilizing	0.841	D	0.643	neutral	None	None	None	None	I
C/M	0.6463	likely_pathogenic	0.6026	pathogenic	-0.031	Destabilizing	0.998	D	0.668	prob.neutral	None	None	None	None	I
C/N	0.6766	likely_pathogenic	0.6295	pathogenic	-1.056	Destabilizing	0.974	D	0.875	deleterious	None	None	None	None	I
C/P	0.9884	likely_pathogenic	0.9838	pathogenic	-1.074	Destabilizing	0.974	D	0.872	deleterious	None	None	None	None	I
C/Q	0.6395	likely_pathogenic	0.5702	pathogenic	-0.908	Destabilizing	0.974	D	0.863	deleterious	None	None	None	None	I
C/R	0.4725	ambiguous	0.4138	ambiguous	-0.994	Destabilizing	0.966	D	0.869	deleterious	N	0.473685088	None	None	I
C/S	0.3134	likely_benign	0.2646	benign	-1.553	Destabilizing	0.666	D	0.683	prob.neutral	N	0.36637033	None	None	I
C/T	0.458	ambiguous	0.4018	ambiguous	-1.235	Destabilizing	0.841	D	0.717	prob.delet.	None	None	None	None	I
C/V	0.4004	ambiguous	0.3626	ambiguous	-1.074	Destabilizing	0.725	D	0.683	prob.neutral	None	None	None	None	I
C/W	0.6621	likely_pathogenic	0.6215	pathogenic	-1.113	Destabilizing	0.997	D	0.786	deleterious	N	0.472375381	None	None	I
C/Y	0.4356	ambiguous	0.3998	ambiguous	-1.04	Destabilizing	0.989	D	0.787	deleterious	N	0.460765586	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.