TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16676	50251;50252;50253	chr2:178612499;178612498;178612497	chr2:179477226;179477225;179477224
N2AB	15035	45328;45329;45330	chr2:178612499;178612498;178612497	chr2:179477226;179477225;179477224
N2A	14108	42547;42548;42549	chr2:178612499;178612498;178612497	chr2:179477226;179477225;179477224
N2B	7611	23056;23057;23058	chr2:178612499;178612498;178612497	chr2:179477226;179477225;179477224
Novex-1	7736	23431;23432;23433	chr2:178612499;178612498;178612497	chr2:179477226;179477225;179477224
Novex-2	7803	23632;23633;23634	chr2:178612499;178612498;178612497	chr2:179477226;179477225;179477224
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-9
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.7414
• 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
E/G	None	None	1.0	N	0.647	0.469	0.460438652622	gnomAD-4.0.0	1.59497E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86251E-06	0	0
E/K	rs759582108	0.665	0.999	N	0.667	0.322	0.383921772103	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/K	rs759582108	0.665	0.999	N	0.667	0.322	0.383921772103	gnomAD-4.0.0	4.78506E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.30182E-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
E/A	0.4222	ambiguous	0.5851	pathogenic	-0.181	Destabilizing	0.999	D	0.651	neutral	N	0.475493775	None	None	I
E/C	0.9805	likely_pathogenic	0.9894	pathogenic	-0.197	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/D	0.3168	likely_benign	0.3009	benign	-0.293	Destabilizing	0.999	D	0.503	neutral	N	0.480675131	None	None	I
E/F	0.9642	likely_pathogenic	0.9809	pathogenic	-0.105	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/G	0.3854	ambiguous	0.5637	ambiguous	-0.335	Destabilizing	1.0	D	0.647	neutral	N	0.481649604	None	None	I
E/H	0.884	likely_pathogenic	0.9355	pathogenic	0.395	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
E/I	0.7793	likely_pathogenic	0.8678	pathogenic	0.18	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/K	0.4735	ambiguous	0.6819	pathogenic	0.363	Stabilizing	0.999	D	0.667	neutral	N	0.478970995	None	None	I
E/L	0.7527	likely_pathogenic	0.8517	pathogenic	0.18	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/M	0.8419	likely_pathogenic	0.9126	pathogenic	0.028	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
E/N	0.6908	likely_pathogenic	0.7731	pathogenic	0.054	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
E/P	0.8222	likely_pathogenic	0.8925	pathogenic	0.079	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
E/Q	0.3705	ambiguous	0.5258	ambiguous	0.078	Stabilizing	1.0	D	0.639	neutral	N	0.467787014	None	None	I
E/R	0.6326	likely_pathogenic	0.7952	pathogenic	0.633	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
E/S	0.5073	ambiguous	0.6323	pathogenic	-0.094	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
E/T	0.6174	likely_pathogenic	0.7419	pathogenic	0.037	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/V	0.5637	ambiguous	0.7084	pathogenic	0.079	Stabilizing	1.0	D	0.713	prob.delet.	N	0.49761147	None	None	I
E/W	0.9838	likely_pathogenic	0.9923	pathogenic	0.002	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/Y	0.9347	likely_pathogenic	0.9654	pathogenic	0.13	Stabilizing	1.0	D	0.688	prob.neutral	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.