TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28929	87010;87011;87012	chr2:178559347;178559346;178559345	chr2:179424074;179424073;179424072
N2AB	27288	82087;82088;82089	chr2:178559347;178559346;178559345	chr2:179424074;179424073;179424072
N2A	26361	79306;79307;79308	chr2:178559347;178559346;178559345	chr2:179424074;179424073;179424072
N2B	19864	59815;59816;59817	chr2:178559347;178559346;178559345	chr2:179424074;179424073;179424072
Novex-1	19989	60190;60191;60192	chr2:178559347;178559346;178559345	chr2:179424074;179424073;179424072
Novex-2	20056	60391;60392;60393	chr2:178559347;178559346;178559345	chr2:179424074;179424073;179424072
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-98
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.4461
• 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
I/K	rs778373815	None	0.014	N	0.413	0.06	0.216624796971	gnomAD-4.0.0	1.20035E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-06	0	0
I/V	None	None	None	N	0.108	0.054	0.132336055621	gnomAD-4.0.0	1.32036E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44376E-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
I/A	0.1344	likely_benign	0.1487	benign	-1.018	Destabilizing	None	N	0.156	neutral	None	None	None	None	N
I/C	0.3561	ambiguous	0.3799	ambiguous	-0.759	Destabilizing	0.245	N	0.37	neutral	None	None	None	None	N
I/D	0.2787	likely_benign	0.2892	benign	-0.242	Destabilizing	0.009	N	0.455	neutral	None	None	None	None	N
I/E	0.2066	likely_benign	0.2228	benign	-0.315	Destabilizing	None	N	0.259	neutral	None	None	None	None	N
I/F	0.1015	likely_benign	0.1054	benign	-0.892	Destabilizing	0.022	N	0.263	neutral	None	None	None	None	N
I/G	0.2784	likely_benign	0.3226	benign	-1.224	Destabilizing	0.009	N	0.376	neutral	None	None	None	None	N
I/H	0.245	likely_benign	0.2607	benign	-0.431	Destabilizing	0.497	N	0.439	neutral	None	None	None	None	N
I/K	0.181	likely_benign	0.1971	benign	-0.474	Destabilizing	0.014	N	0.413	neutral	N	0.337562867	None	None	N
I/L	0.0635	likely_benign	0.0707	benign	-0.582	Destabilizing	None	N	0.095	neutral	N	0.336696075	None	None	N
I/M	0.0692	likely_benign	0.0695	benign	-0.485	Destabilizing	0.033	N	0.35	neutral	N	0.397515248	None	None	N
I/N	0.1	likely_benign	0.1131	benign	-0.259	Destabilizing	0.085	N	0.525	neutral	None	None	None	None	N
I/P	0.3245	likely_benign	0.3697	ambiguous	-0.693	Destabilizing	0.085	N	0.486	neutral	None	None	None	None	N
I/Q	0.1626	likely_benign	0.1793	benign	-0.512	Destabilizing	0.044	N	0.497	neutral	None	None	None	None	N
I/R	0.1678	likely_benign	0.177	benign	0.109	Stabilizing	0.033	N	0.488	neutral	N	0.367365699	None	None	N
I/S	0.1115	likely_benign	0.1288	benign	-0.819	Destabilizing	0.009	N	0.363	neutral	None	None	None	None	N
I/T	0.1061	likely_benign	0.1148	benign	-0.782	Destabilizing	0.007	N	0.349	neutral	N	0.359380934	None	None	N
I/V	0.0559	likely_benign	0.0553	benign	-0.693	Destabilizing	None	N	0.108	neutral	N	0.319707825	None	None	N
I/W	0.5725	likely_pathogenic	0.5924	pathogenic	-0.856	Destabilizing	0.788	D	0.426	neutral	None	None	None	None	N
I/Y	0.2742	likely_benign	0.3025	benign	-0.618	Destabilizing	0.085	N	0.442	neutral	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.