TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21617	65074;65075;65076	chr2:178584792;178584791;178584790	chr2:179449519;179449518;179449517
N2AB	19976	60151;60152;60153	chr2:178584792;178584791;178584790	chr2:179449519;179449518;179449517
N2A	19049	57370;57371;57372	chr2:178584792;178584791;178584790	chr2:179449519;179449518;179449517
N2B	12552	37879;37880;37881	chr2:178584792;178584791;178584790	chr2:179449519;179449518;179449517
Novex-1	12677	38254;38255;38256	chr2:178584792;178584791;178584790	chr2:179449519;179449518;179449517
Novex-2	12744	38455;38456;38457	chr2:178584792;178584791;178584790	chr2:179449519;179449518;179449517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-44
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2436
• 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
T/I	rs1455243319	0.085	0.978	N	0.757	0.505	0.428630128466	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/I	rs1455243319	0.085	0.978	N	0.757	0.505	0.428630128466	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1455243319	0.085	0.978	N	0.757	0.505	0.428630128466	gnomAD-4.0.0	6.57704E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47106E-05	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	0.141	likely_benign	0.1694	benign	-0.834	Destabilizing	0.039	N	0.332	neutral	N	0.495513427	None	None	I
T/C	0.4966	ambiguous	0.5325	ambiguous	-0.396	Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	I
T/D	0.7306	likely_pathogenic	0.7643	pathogenic	-0.014	Destabilizing	0.992	D	0.757	deleterious	None	None	None	None	I
T/E	0.6084	likely_pathogenic	0.6612	pathogenic	0.125	Stabilizing	0.983	D	0.714	prob.delet.	None	None	None	None	I
T/F	0.6293	likely_pathogenic	0.6945	pathogenic	-0.803	Destabilizing	0.992	D	0.769	deleterious	None	None	None	None	I
T/G	0.409	ambiguous	0.4405	ambiguous	-1.186	Destabilizing	0.895	D	0.618	neutral	None	None	None	None	I
T/H	0.5212	ambiguous	0.5803	pathogenic	-1.165	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
T/I	0.4639	ambiguous	0.533	ambiguous	0.053	Stabilizing	0.978	D	0.757	deleterious	N	0.497070363	None	None	I
T/K	0.3918	ambiguous	0.4422	ambiguous	0.001	Stabilizing	0.983	D	0.703	prob.neutral	None	None	None	None	I
T/L	0.1614	likely_benign	0.2063	benign	0.053	Stabilizing	0.895	D	0.551	neutral	None	None	None	None	I
T/M	0.1323	likely_benign	0.1635	benign	-0.042	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
T/N	0.1702	likely_benign	0.2026	benign	-0.464	Destabilizing	0.989	D	0.712	prob.delet.	N	0.482422375	None	None	I
T/P	0.1324	likely_benign	0.1642	benign	-0.211	Destabilizing	0.989	D	0.769	deleterious	N	0.471800085	None	None	I
T/Q	0.3665	ambiguous	0.4215	ambiguous	-0.319	Destabilizing	0.992	D	0.783	deleterious	None	None	None	None	I
T/R	0.3476	ambiguous	0.3959	ambiguous	-0.094	Destabilizing	0.983	D	0.762	deleterious	None	None	None	None	I
T/S	0.2071	likely_benign	0.2294	benign	-0.853	Destabilizing	0.865	D	0.457	neutral	N	0.494752959	None	None	I
T/V	0.315	likely_benign	0.3669	ambiguous	-0.211	Destabilizing	0.895	D	0.471	neutral	None	None	None	None	I
T/W	0.8779	likely_pathogenic	0.8922	pathogenic	-0.842	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
T/Y	0.5752	likely_pathogenic	0.6243	pathogenic	-0.464	Destabilizing	0.997	D	0.775	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.