TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24904	74935;74936;74937	chr2:178571422;178571421;178571420	chr2:179436149;179436148;179436147
N2AB	23263	70012;70013;70014	chr2:178571422;178571421;178571420	chr2:179436149;179436148;179436147
N2A	22336	67231;67232;67233	chr2:178571422;178571421;178571420	chr2:179436149;179436148;179436147
N2B	15839	47740;47741;47742	chr2:178571422;178571421;178571420	chr2:179436149;179436148;179436147
Novex-1	15964	48115;48116;48117	chr2:178571422;178571421;178571420	chr2:179436149;179436148;179436147
Novex-2	16031	48316;48317;48318	chr2:178571422;178571421;178571420	chr2:179436149;179436148;179436147
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-68
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.9019
• 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
Y/C	None	None	0.994	N	0.867	0.289	0.551550886788	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	6.07533E-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
Y/A	0.9631	likely_pathogenic	0.9624	pathogenic	-0.589	Destabilizing	0.74	D	0.582	neutral	None	None	None	None	N
Y/C	0.8178	likely_pathogenic	0.8063	pathogenic	0.155	Stabilizing	0.994	D	0.867	deleterious	N	0.476009458	None	None	N
Y/D	0.8937	likely_pathogenic	0.8881	pathogenic	0.766	Stabilizing	0.883	D	0.833	deleterious	N	0.472415651	None	None	N
Y/E	0.9842	likely_pathogenic	0.9851	pathogenic	0.746	Stabilizing	0.909	D	0.623	neutral	None	None	None	None	N
Y/F	0.2094	likely_benign	0.2113	benign	-0.296	Destabilizing	0.007	N	0.344	neutral	N	0.481832355	None	None	N
Y/G	0.9573	likely_pathogenic	0.9554	pathogenic	-0.772	Destabilizing	0.909	D	0.608	neutral	None	None	None	None	N
Y/H	0.644	likely_pathogenic	0.6242	pathogenic	0.224	Stabilizing	0.015	N	0.401	neutral	N	0.493599	None	None	N
Y/I	0.9329	likely_pathogenic	0.9328	pathogenic	-0.132	Destabilizing	0.909	D	0.568	neutral	None	None	None	None	N
Y/K	0.9809	likely_pathogenic	0.9807	pathogenic	0.19	Stabilizing	0.909	D	0.799	deleterious	None	None	None	None	N
Y/L	0.7621	likely_pathogenic	0.7591	pathogenic	-0.132	Destabilizing	0.587	D	0.605	neutral	None	None	None	None	N
Y/M	0.9226	likely_pathogenic	0.9247	pathogenic	-0.058	Destabilizing	0.996	D	0.546	neutral	None	None	None	None	N
Y/N	0.7027	likely_pathogenic	0.7239	pathogenic	-0.033	Destabilizing	0.883	D	0.837	deleterious	N	0.490270693	None	None	N
Y/P	0.9658	likely_pathogenic	0.9607	pathogenic	-0.266	Destabilizing	0.984	D	0.837	deleterious	None	None	None	None	N
Y/Q	0.9765	likely_pathogenic	0.9766	pathogenic	0.028	Stabilizing	0.909	D	0.573	neutral	None	None	None	None	N
Y/R	0.9736	likely_pathogenic	0.9707	pathogenic	0.402	Stabilizing	0.909	D	0.843	deleterious	None	None	None	None	N
Y/S	0.8586	likely_pathogenic	0.8433	pathogenic	-0.398	Destabilizing	0.883	D	0.575	neutral	N	0.504469355	None	None	N
Y/T	0.9651	likely_pathogenic	0.9657	pathogenic	-0.327	Destabilizing	0.953	D	0.782	deleterious	None	None	None	None	N
Y/V	0.919	likely_pathogenic	0.9182	pathogenic	-0.266	Destabilizing	0.74	D	0.585	neutral	None	None	None	None	N
Y/W	0.7501	likely_pathogenic	0.7577	pathogenic	-0.46	Destabilizing	0.996	D	0.563	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.