TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20637	62134;62135;62136	chr2:178589816;178589815;178589814	chr2:179454543;179454542;179454541
N2AB	18996	57211;57212;57213	chr2:178589816;178589815;178589814	chr2:179454543;179454542;179454541
N2A	18069	54430;54431;54432	chr2:178589816;178589815;178589814	chr2:179454543;179454542;179454541
N2B	11572	34939;34940;34941	chr2:178589816;178589815;178589814	chr2:179454543;179454542;179454541
Novex-1	11697	35314;35315;35316	chr2:178589816;178589815;178589814	chr2:179454543;179454542;179454541
Novex-2	11764	35515;35516;35517	chr2:178589816;178589815;178589814	chr2:179454543;179454542;179454541
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: Fn3-37
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.3319
• 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/V	None	None	1.0	N	0.793	0.544	0.627796283164	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85945E-06	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	0.4346	ambiguous	0.3636	ambiguous	-0.436	Destabilizing	0.999	D	0.696	prob.neutral	N	0.487880105	None	None	N
E/C	0.9638	likely_pathogenic	0.9441	pathogenic	-0.274	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/D	0.5864	likely_pathogenic	0.5908	pathogenic	-1.238	Destabilizing	0.999	D	0.485	neutral	N	0.476839741	None	None	N
E/F	0.9766	likely_pathogenic	0.9632	pathogenic	0.442	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/G	0.6439	likely_pathogenic	0.5693	pathogenic	-0.891	Destabilizing	1.0	D	0.763	deleterious	N	0.486994732	None	None	N
E/H	0.914	likely_pathogenic	0.881	pathogenic	0.114	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/I	0.8154	likely_pathogenic	0.7313	pathogenic	0.835	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/K	0.6443	likely_pathogenic	0.5236	ambiguous	-0.669	Destabilizing	0.999	D	0.589	neutral	N	0.520308386	None	None	N
E/L	0.8797	likely_pathogenic	0.8158	pathogenic	0.835	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/M	0.8483	likely_pathogenic	0.7973	pathogenic	1.286	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/N	0.7762	likely_pathogenic	0.7418	pathogenic	-1.282	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/P	0.8627	likely_pathogenic	0.8153	pathogenic	0.434	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Q	0.3807	ambiguous	0.3332	benign	-1.019	Destabilizing	1.0	D	0.627	neutral	N	0.473864	None	None	N
E/R	0.7866	likely_pathogenic	0.7032	pathogenic	-0.401	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/S	0.5319	ambiguous	0.496	ambiguous	-1.682	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
E/T	0.5973	likely_pathogenic	0.5141	ambiguous	-1.287	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/V	0.6605	likely_pathogenic	0.5517	ambiguous	0.434	Stabilizing	1.0	D	0.793	deleterious	N	0.482146113	None	None	N
E/W	0.9937	likely_pathogenic	0.9902	pathogenic	0.608	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.9503	likely_pathogenic	0.9265	pathogenic	0.693	Stabilizing	1.0	D	0.787	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.