TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17195	51808;51809;51810	chr2:178609840;178609839;178609838	chr2:179474567;179474566;179474565
N2AB	15554	46885;46886;46887	chr2:178609840;178609839;178609838	chr2:179474567;179474566;179474565
N2A	14627	44104;44105;44106	chr2:178609840;178609839;178609838	chr2:179474567;179474566;179474565
N2B	8130	24613;24614;24615	chr2:178609840;178609839;178609838	chr2:179474567;179474566;179474565
Novex-1	8255	24988;24989;24990	chr2:178609840;178609839;178609838	chr2:179474567;179474566;179474565
Novex-2	8322	25189;25190;25191	chr2:178609840;178609839;178609838	chr2:179474567;179474566;179474565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-13
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.5974
• 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
K/N	None	None	0.801	N	0.259	0.128	0.168933306366	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
K/A	0.3379	likely_benign	0.3114	benign	-0.629	Destabilizing	0.688	D	0.317	neutral	None	None	None	None	N
K/C	0.6164	likely_pathogenic	0.5664	pathogenic	-0.563	Destabilizing	0.998	D	0.299	neutral	None	None	None	None	N
K/D	0.5901	likely_pathogenic	0.5599	ambiguous	-0.408	Destabilizing	0.525	D	0.315	neutral	None	None	None	None	N
K/E	0.1336	likely_benign	0.1254	benign	-0.255	Destabilizing	0.002	N	0.125	neutral	N	0.412700918	None	None	N
K/F	0.673	likely_pathogenic	0.637	pathogenic	-0.028	Destabilizing	0.991	D	0.287	neutral	None	None	None	None	N
K/G	0.5055	ambiguous	0.4722	ambiguous	-1.031	Destabilizing	0.842	D	0.3	neutral	None	None	None	None	N
K/H	0.2455	likely_benign	0.2237	benign	-1.221	Destabilizing	0.974	D	0.31	neutral	None	None	None	None	N
K/I	0.1977	likely_benign	0.188	benign	0.439	Stabilizing	0.974	D	0.31	neutral	None	None	None	None	N
K/L	0.2842	likely_benign	0.2708	benign	0.439	Stabilizing	0.842	D	0.311	neutral	None	None	None	None	N
K/M	0.187	likely_benign	0.1773	benign	0.13	Stabilizing	0.989	D	0.31	neutral	N	0.469420992	None	None	N
K/N	0.3777	ambiguous	0.3605	ambiguous	-0.749	Destabilizing	0.801	D	0.259	neutral	N	0.501375908	None	None	N
K/P	0.9574	likely_pathogenic	0.9556	pathogenic	0.111	Stabilizing	0.915	D	0.322	neutral	None	None	None	None	N
K/Q	0.0923	likely_benign	0.0852	benign	-0.668	Destabilizing	0.136	N	0.124	neutral	N	0.413391564	None	None	N
K/R	0.0928	likely_benign	0.0893	benign	-0.81	Destabilizing	0.625	D	0.314	neutral	N	0.444869264	None	None	N
K/S	0.3622	ambiguous	0.34	ambiguous	-1.283	Destabilizing	0.688	D	0.289	neutral	None	None	None	None	N
K/T	0.1399	likely_benign	0.1313	benign	-0.921	Destabilizing	0.801	D	0.301	neutral	N	0.44352247	None	None	N
K/V	0.175	likely_benign	0.165	benign	0.111	Stabilizing	0.915	D	0.289	neutral	None	None	None	None	N
K/W	0.7302	likely_pathogenic	0.7023	pathogenic	0.014	Stabilizing	0.998	D	0.309	neutral	None	None	None	None	N
K/Y	0.5834	likely_pathogenic	0.5445	ambiguous	0.255	Stabilizing	0.991	D	0.297	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.