TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34439	103540;103541;103542	chr2:178533300;178533299;178533298	chr2:179398027;179398026;179398025
N2AB	32798	98617;98618;98619	chr2:178533300;178533299;178533298	chr2:179398027;179398026;179398025
N2A	31871	95836;95837;95838	chr2:178533300;178533299;178533298	chr2:179398027;179398026;179398025
N2B	25374	76345;76346;76347	chr2:178533300;178533299;178533298	chr2:179398027;179398026;179398025
Novex-1	25499	76720;76721;76722	chr2:178533300;178533299;178533298	chr2:179398027;179398026;179398025
Novex-2	25566	76921;76922;76923	chr2:178533300;178533299;178533298	chr2:179398027;179398026;179398025
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: Ig-162
• Domain position: 77
• Structural Position: 159
• Q(SASA): 0.31
• 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	None	None	1.0	N	0.816	0.568	0.660119374745	gnomAD-4.0.0	6.84158E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99405E-07	0	0
T/S	None	None	0.999	N	0.635	0.352	0.349870743963	gnomAD-4.0.0	6.84158E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-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
T/A	0.1983	likely_benign	0.1519	benign	-0.649	Destabilizing	0.999	D	0.627	neutral	D	0.5283658	None	None	I
T/C	0.7362	likely_pathogenic	0.6379	pathogenic	-0.675	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
T/D	0.8373	likely_pathogenic	0.7454	pathogenic	-1.421	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
T/E	0.5872	likely_pathogenic	0.5035	ambiguous	-1.414	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
T/F	0.6436	likely_pathogenic	0.5088	ambiguous	-0.986	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
T/G	0.6379	likely_pathogenic	0.5257	ambiguous	-0.874	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
T/H	0.5839	likely_pathogenic	0.4633	ambiguous	-1.303	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
T/I	0.4531	ambiguous	0.3435	ambiguous	-0.142	Destabilizing	1.0	D	0.816	deleterious	N	0.489534806	None	None	I
T/K	0.4782	ambiguous	0.3772	ambiguous	-0.718	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
T/L	0.3464	ambiguous	0.2508	benign	-0.142	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
T/M	0.2018	likely_benign	0.1509	benign	0.272	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
T/N	0.4248	ambiguous	0.3149	benign	-0.93	Destabilizing	1.0	D	0.812	deleterious	D	0.535254487	None	None	I
T/P	0.9265	likely_pathogenic	0.8989	pathogenic	-0.281	Destabilizing	1.0	D	0.803	deleterious	D	0.534137107	None	None	I
T/Q	0.4067	ambiguous	0.3268	benign	-1.229	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
T/R	0.4108	ambiguous	0.3271	benign	-0.414	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
T/S	0.2213	likely_benign	0.1621	benign	-0.997	Destabilizing	0.999	D	0.635	neutral	N	0.483940233	None	None	I
T/V	0.2964	likely_benign	0.2224	benign	-0.281	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
T/W	0.898	likely_pathogenic	0.8512	pathogenic	-1.011	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
T/Y	0.7146	likely_pathogenic	0.6049	pathogenic	-0.668	Destabilizing	1.0	D	0.84	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.