TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19323	58192;58193;58194	chr2:178594527;178594526;178594525	chr2:179459254;179459253;179459252
N2AB	17682	53269;53270;53271	chr2:178594527;178594526;178594525	chr2:179459254;179459253;179459252
N2A	16755	50488;50489;50490	chr2:178594527;178594526;178594525	chr2:179459254;179459253;179459252
N2B	10258	30997;30998;30999	chr2:178594527;178594526;178594525	chr2:179459254;179459253;179459252
Novex-1	10383	31372;31373;31374	chr2:178594527;178594526;178594525	chr2:179459254;179459253;179459252
Novex-2	10450	31573;31574;31575	chr2:178594527;178594526;178594525	chr2:179459254;179459253;179459252
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-28
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1295
• 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
S/R	None	None	0.966	N	0.808	0.289	0.190952846119	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.1028	likely_benign	0.1043	benign	-0.798	Destabilizing	0.067	N	0.351	neutral	None	None	None	None	N
S/C	0.1003	likely_benign	0.094	benign	-0.492	Destabilizing	0.028	N	0.648	neutral	N	0.492734995	None	None	N
S/D	0.8697	likely_pathogenic	0.8304	pathogenic	-1.85	Destabilizing	0.915	D	0.763	deleterious	None	None	None	None	N
S/E	0.8027	likely_pathogenic	0.7673	pathogenic	-1.58	Destabilizing	0.915	D	0.761	deleterious	None	None	None	None	N
S/F	0.5185	ambiguous	0.3839	ambiguous	-0.453	Destabilizing	0.974	D	0.809	deleterious	None	None	None	None	N
S/G	0.1732	likely_benign	0.1585	benign	-1.216	Destabilizing	0.801	D	0.708	prob.delet.	N	0.480000558	None	None	N
S/H	0.542	ambiguous	0.4571	ambiguous	-1.415	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
S/I	0.4852	ambiguous	0.3768	ambiguous	0.304	Stabilizing	0.669	D	0.727	prob.delet.	N	0.438479223	None	None	N
S/K	0.852	likely_pathogenic	0.8023	pathogenic	-0.142	Destabilizing	0.915	D	0.757	deleterious	None	None	None	None	N
S/L	0.3018	likely_benign	0.234	benign	0.304	Stabilizing	0.728	D	0.724	prob.delet.	None	None	None	None	N
S/M	0.3054	likely_benign	0.2628	benign	-0.066	Destabilizing	0.974	D	0.797	deleterious	None	None	None	None	N
S/N	0.3959	ambiguous	0.3341	benign	-1.089	Destabilizing	0.966	D	0.779	deleterious	N	0.47012779	None	None	N
S/P	0.9946	likely_pathogenic	0.9931	pathogenic	-0.033	Destabilizing	0.974	D	0.792	deleterious	None	None	None	None	N
S/Q	0.6209	likely_pathogenic	0.6005	pathogenic	-0.615	Destabilizing	0.991	D	0.768	deleterious	None	None	None	None	N
S/R	0.8191	likely_pathogenic	0.7538	pathogenic	-0.737	Destabilizing	0.966	D	0.808	deleterious	N	0.369139355	None	None	N
S/T	0.1501	likely_benign	0.1283	benign	-0.642	Destabilizing	0.051	N	0.457	neutral	N	0.475362743	None	None	N
S/V	0.3777	ambiguous	0.3168	benign	-0.033	Destabilizing	0.067	N	0.683	prob.neutral	None	None	None	None	N
S/W	0.6594	likely_pathogenic	0.5437	ambiguous	-0.928	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
S/Y	0.3522	ambiguous	0.2459	benign	-0.409	Destabilizing	0.991	D	0.794	deleterious	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.