TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24138	72637;72638;72639	chr2:178573720;178573719;178573718	chr2:179438447;179438446;179438445
N2AB	22497	67714;67715;67716	chr2:178573720;178573719;178573718	chr2:179438447;179438446;179438445
N2A	21570	64933;64934;64935	chr2:178573720;178573719;178573718	chr2:179438447;179438446;179438445
N2B	15073	45442;45443;45444	chr2:178573720;178573719;178573718	chr2:179438447;179438446;179438445
Novex-1	15198	45817;45818;45819	chr2:178573720;178573719;178573718	chr2:179438447;179438446;179438445
Novex-2	15265	46018;46019;46020	chr2:178573720;178573719;178573718	chr2:179438447;179438446;179438445
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: Fn3-63
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.4843
• 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
E/G	rs776517983	-1.264	0.999	D	0.713	0.423	0.444706120422	gnomAD-2.1.1	5.01E-06	None	None	None	None	N	None	0	0	None	0	6.09E-05	None	0	None	0	0	0
E/V	None	None	1.0	N	0.78	0.493	0.567026466452	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
E/A	0.5214	ambiguous	0.6121	pathogenic	-0.751	Destabilizing	0.998	D	0.664	neutral	N	0.471279879	None	None	N
E/C	0.9633	likely_pathogenic	0.9786	pathogenic	-0.134	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/D	0.2094	likely_benign	0.2435	benign	-0.635	Destabilizing	0.434	N	0.205	neutral	N	0.458161062	None	None	N
E/F	0.9651	likely_pathogenic	0.9783	pathogenic	-0.599	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/G	0.3839	ambiguous	0.4536	ambiguous	-1.007	Destabilizing	0.999	D	0.713	prob.delet.	D	0.523289976	None	None	N
E/H	0.8312	likely_pathogenic	0.8847	pathogenic	-0.741	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
E/I	0.8574	likely_pathogenic	0.9047	pathogenic	-0.085	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/K	0.4531	ambiguous	0.5282	ambiguous	-0.025	Destabilizing	0.998	D	0.579	neutral	N	0.468379817	None	None	N
E/L	0.8259	likely_pathogenic	0.8804	pathogenic	-0.085	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/M	0.85	likely_pathogenic	0.8939	pathogenic	0.307	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/N	0.5355	ambiguous	0.6496	pathogenic	-0.363	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.9817	likely_pathogenic	0.9843	pathogenic	-0.287	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/Q	0.3369	likely_benign	0.3956	ambiguous	-0.324	Destabilizing	0.999	D	0.681	prob.neutral	N	0.473748641	None	None	N
E/R	0.6171	likely_pathogenic	0.6786	pathogenic	0.09	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/S	0.4876	ambiguous	0.5873	pathogenic	-0.582	Destabilizing	0.997	D	0.626	neutral	None	None	None	None	N
E/T	0.5607	ambiguous	0.6528	pathogenic	-0.371	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/V	0.6904	likely_pathogenic	0.7724	pathogenic	-0.287	Destabilizing	1.0	D	0.78	deleterious	N	0.487333446	None	None	N
E/W	0.9823	likely_pathogenic	0.9891	pathogenic	-0.402	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.9228	likely_pathogenic	0.9524	pathogenic	-0.349	Destabilizing	1.0	D	0.756	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.