TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18559	55900;55901;55902	chr2:178601322;178601321;178601320	chr2:179466049;179466048;179466047
N2AB	16918	50977;50978;50979	chr2:178601322;178601321;178601320	chr2:179466049;179466048;179466047
N2A	15991	48196;48197;48198	chr2:178601322;178601321;178601320	chr2:179466049;179466048;179466047
N2B	9494	28705;28706;28707	chr2:178601322;178601321;178601320	chr2:179466049;179466048;179466047
Novex-1	9619	29080;29081;29082	chr2:178601322;178601321;178601320	chr2:179466049;179466048;179466047
Novex-2	9686	29281;29282;29283	chr2:178601322;178601321;178601320	chr2:179466049;179466048;179466047
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-22
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.6436
• 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
F/V	None	None	0.704	N	0.413	0.213	0.481915485015	gnomAD-4.0.0	1.60617E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88947E-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
F/A	0.7653	likely_pathogenic	0.7412	pathogenic	-1.115	Destabilizing	0.927	D	0.485	neutral	None	None	None	None	I
F/C	0.3733	ambiguous	0.3506	ambiguous	-0.337	Destabilizing	0.999	D	0.542	neutral	N	0.472207794	None	None	I
F/D	0.9193	likely_pathogenic	0.9231	pathogenic	0.564	Stabilizing	0.964	D	0.53	neutral	None	None	None	None	I
F/E	0.9207	likely_pathogenic	0.9269	pathogenic	0.548	Stabilizing	0.982	D	0.531	neutral	None	None	None	None	I
F/G	0.8802	likely_pathogenic	0.8883	pathogenic	-1.324	Destabilizing	0.939	D	0.519	neutral	None	None	None	None	I
F/H	0.5232	ambiguous	0.5545	ambiguous	0.127	Stabilizing	0.991	D	0.485	neutral	None	None	None	None	I
F/I	0.4672	ambiguous	0.4236	ambiguous	-0.572	Destabilizing	0.852	D	0.324	neutral	N	0.428166229	None	None	I
F/K	0.9312	likely_pathogenic	0.9385	pathogenic	-0.19	Destabilizing	0.939	D	0.525	neutral	None	None	None	None	I
F/L	0.9002	likely_pathogenic	0.8906	pathogenic	-0.572	Destabilizing	0.015	N	0.177	neutral	N	0.439634016	None	None	I
F/M	0.667	likely_pathogenic	0.6524	pathogenic	-0.421	Destabilizing	0.982	D	0.383	neutral	None	None	None	None	I
F/N	0.6854	likely_pathogenic	0.7255	pathogenic	-0.133	Destabilizing	0.17	N	0.41	neutral	None	None	None	None	I
F/P	0.9951	likely_pathogenic	0.9947	pathogenic	-0.735	Destabilizing	0.997	D	0.545	neutral	None	None	None	None	I
F/Q	0.8497	likely_pathogenic	0.8521	pathogenic	-0.211	Destabilizing	0.991	D	0.547	neutral	None	None	None	None	I
F/R	0.8704	likely_pathogenic	0.8756	pathogenic	0.328	Stabilizing	0.991	D	0.548	neutral	None	None	None	None	I
F/S	0.6603	likely_pathogenic	0.6327	pathogenic	-0.821	Destabilizing	0.92	D	0.515	neutral	N	0.48167264	None	None	I
F/T	0.7979	likely_pathogenic	0.7872	pathogenic	-0.744	Destabilizing	0.939	D	0.507	neutral	None	None	None	None	I
F/V	0.4695	ambiguous	0.4267	ambiguous	-0.735	Destabilizing	0.704	D	0.413	neutral	N	0.42443249	None	None	I
F/W	0.4231	ambiguous	0.4479	ambiguous	-0.353	Destabilizing	0.999	D	0.431	neutral	None	None	None	None	I
F/Y	0.1426	likely_benign	0.1533	benign	-0.353	Destabilizing	0.986	D	0.365	neutral	N	0.445194551	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.