TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26179	78760;78761;78762	chr2:178567597;178567596;178567595	chr2:179432324;179432323;179432322
N2AB	24538	73837;73838;73839	chr2:178567597;178567596;178567595	chr2:179432324;179432323;179432322
N2A	23611	71056;71057;71058	chr2:178567597;178567596;178567595	chr2:179432324;179432323;179432322
N2B	17114	51565;51566;51567	chr2:178567597;178567596;178567595	chr2:179432324;179432323;179432322
Novex-1	17239	51940;51941;51942	chr2:178567597;178567596;178567595	chr2:179432324;179432323;179432322
Novex-2	17306	52141;52142;52143	chr2:178567597;178567596;178567595	chr2:179432324;179432323;179432322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-78
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.29
• 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
T/N	None	None	0.986	N	0.717	0.341	0.266843984389	gnomAD-4.0.0	1.5965E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86829E-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
T/A	0.2977	likely_benign	0.2963	benign	-1.022	Destabilizing	0.802	D	0.618	neutral	N	0.454193949	None	None	N
T/C	0.717	likely_pathogenic	0.6937	pathogenic	-0.748	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
T/D	0.971	likely_pathogenic	0.9738	pathogenic	-1.101	Destabilizing	0.989	D	0.721	deleterious	None	None	None	None	N
T/E	0.971	likely_pathogenic	0.977	pathogenic	-0.937	Destabilizing	0.989	D	0.716	prob.delet.	None	None	None	None	N
T/F	0.9518	likely_pathogenic	0.9561	pathogenic	-0.676	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
T/G	0.7276	likely_pathogenic	0.7244	pathogenic	-1.431	Destabilizing	0.929	D	0.745	deleterious	None	None	None	None	N
T/H	0.939	likely_pathogenic	0.9492	pathogenic	-1.601	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
T/I	0.8346	likely_pathogenic	0.8444	pathogenic	0.034	Stabilizing	0.993	D	0.807	deleterious	N	0.456458447	None	None	N
T/K	0.9605	likely_pathogenic	0.9685	pathogenic	-0.64	Destabilizing	0.989	D	0.709	prob.delet.	None	None	None	None	N
T/L	0.6232	likely_pathogenic	0.6412	pathogenic	0.034	Stabilizing	0.963	D	0.694	prob.delet.	None	None	None	None	N
T/M	0.4708	ambiguous	0.4974	ambiguous	0.037	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/N	0.8114	likely_pathogenic	0.8352	pathogenic	-1.163	Destabilizing	0.986	D	0.717	prob.delet.	N	0.494329706	None	None	N
T/P	0.8569	likely_pathogenic	0.8661	pathogenic	-0.285	Destabilizing	0.993	D	0.796	deleterious	N	0.462400384	None	None	N
T/Q	0.9344	likely_pathogenic	0.9476	pathogenic	-0.998	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
T/R	0.9407	likely_pathogenic	0.9519	pathogenic	-0.774	Destabilizing	0.989	D	0.792	deleterious	None	None	None	None	N
T/S	0.1915	likely_benign	0.1826	benign	-1.41	Destabilizing	0.208	N	0.399	neutral	N	0.423805267	None	None	N
T/V	0.5988	likely_pathogenic	0.6021	pathogenic	-0.285	Destabilizing	0.963	D	0.614	neutral	None	None	None	None	N
T/W	0.9893	likely_pathogenic	0.9905	pathogenic	-0.784	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/Y	0.9631	likely_pathogenic	0.9684	pathogenic	-0.434	Destabilizing	0.998	D	0.865	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.