TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30413	91462;91463;91464	chr2:178551663;178551662;178551661	chr2:179416390;179416389;179416388
N2AB	28772	86539;86540;86541	chr2:178551663;178551662;178551661	chr2:179416390;179416389;179416388
N2A	27845	83758;83759;83760	chr2:178551663;178551662;178551661	chr2:179416390;179416389;179416388
N2B	21348	64267;64268;64269	chr2:178551663;178551662;178551661	chr2:179416390;179416389;179416388
Novex-1	21473	64642;64643;64644	chr2:178551663;178551662;178551661	chr2:179416390;179416389;179416388
Novex-2	21540	64843;64844;64845	chr2:178551663;178551662;178551661	chr2:179416390;179416389;179416388
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-109
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.157
• 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
P/S	None	None	0.953	N	0.609	0.236	0.232513804876	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
P/A	0.0553	likely_benign	0.0585	benign	-1.728	Destabilizing	0.953	D	0.591	neutral	N	0.481325923	None	None	N
P/C	0.3645	ambiguous	0.3774	ambiguous	-1.121	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/D	0.7254	likely_pathogenic	0.7298	pathogenic	-1.708	Destabilizing	0.964	D	0.607	neutral	None	None	None	None	N
P/E	0.4653	ambiguous	0.4786	ambiguous	-1.699	Destabilizing	0.931	D	0.582	neutral	None	None	None	None	N
P/F	0.5124	ambiguous	0.5434	ambiguous	-1.389	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
P/G	0.3751	ambiguous	0.3785	ambiguous	-2.057	Highly Destabilizing	0.982	D	0.656	prob.neutral	None	None	None	None	N
P/H	0.3382	likely_benign	0.3547	ambiguous	-1.533	Destabilizing	0.999	D	0.695	prob.delet.	None	None	None	None	N
P/I	0.1913	likely_benign	0.2022	benign	-0.911	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
P/K	0.5846	likely_pathogenic	0.6104	pathogenic	-1.31	Destabilizing	0.931	D	0.593	neutral	None	None	None	None	N
P/L	0.1467	likely_benign	0.1574	benign	-0.911	Destabilizing	0.986	D	0.736	deleterious	N	0.520209598	None	None	N
P/M	0.2812	likely_benign	0.2858	benign	-0.659	Destabilizing	1.0	D	0.7	prob.delet.	None	None	None	None	N
P/N	0.4344	ambiguous	0.4359	ambiguous	-1.137	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
P/Q	0.2525	likely_benign	0.2628	benign	-1.337	Destabilizing	0.441	N	0.412	neutral	N	0.468353364	None	None	N
P/R	0.4471	ambiguous	0.4821	ambiguous	-0.741	Destabilizing	0.986	D	0.6	neutral	N	0.49485141	None	None	N
P/S	0.1244	likely_benign	0.1248	benign	-1.671	Destabilizing	0.953	D	0.609	neutral	N	0.521017675	None	None	N
P/T	0.0919	likely_benign	0.0915	benign	-1.555	Destabilizing	0.976	D	0.603	neutral	N	0.51060868	None	None	N
P/V	0.1321	likely_benign	0.1385	benign	-1.15	Destabilizing	0.995	D	0.633	neutral	None	None	None	None	N
P/W	0.8166	likely_pathogenic	0.8362	pathogenic	-1.576	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/Y	0.5611	ambiguous	0.5987	pathogenic	-1.295	Destabilizing	0.998	D	0.783	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.