TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26716	80371;80372;80373	chr2:178565986;178565985;178565984	chr2:179430713;179430712;179430711
N2AB	25075	75448;75449;75450	chr2:178565986;178565985;178565984	chr2:179430713;179430712;179430711
N2A	24148	72667;72668;72669	chr2:178565986;178565985;178565984	chr2:179430713;179430712;179430711
N2B	17651	53176;53177;53178	chr2:178565986;178565985;178565984	chr2:179430713;179430712;179430711
Novex-1	17776	53551;53552;53553	chr2:178565986;178565985;178565984	chr2:179430713;179430712;179430711
Novex-2	17843	53752;53753;53754	chr2:178565986;178565985;178565984	chr2:179430713;179430712;179430711
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-82
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4157
• 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
K/E	rs902372912	None	0.557	N	0.553	0.287	0.28722502521	gnomAD-4.0.0	9.57999E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.25938E-05	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
K/A	0.5486	ambiguous	0.5779	pathogenic	-0.17	Destabilizing	0.735	D	0.569	neutral	None	None	None	None	I
K/C	0.6916	likely_pathogenic	0.7424	pathogenic	-0.173	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	I
K/D	0.844	likely_pathogenic	0.8607	pathogenic	-0.057	Destabilizing	0.951	D	0.687	prob.neutral	None	None	None	None	I
K/E	0.3905	ambiguous	0.4309	ambiguous	-0.009	Destabilizing	0.557	D	0.553	neutral	N	0.49923968	None	None	I
K/F	0.8625	likely_pathogenic	0.8864	pathogenic	-0.068	Destabilizing	0.94	D	0.797	deleterious	None	None	None	None	I
K/G	0.6511	likely_pathogenic	0.6706	pathogenic	-0.466	Destabilizing	0.951	D	0.653	neutral	None	None	None	None	I
K/H	0.3803	ambiguous	0.4218	ambiguous	-0.834	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	I
K/I	0.4303	ambiguous	0.4631	ambiguous	0.558	Stabilizing	0.364	N	0.793	deleterious	None	None	None	None	I
K/L	0.4576	ambiguous	0.4905	ambiguous	0.558	Stabilizing	0.075	N	0.613	neutral	None	None	None	None	I
K/M	0.3336	likely_benign	0.3694	ambiguous	0.41	Stabilizing	0.976	D	0.719	prob.delet.	D	0.524772843	None	None	I
K/N	0.564	ambiguous	0.6316	pathogenic	-0.001	Destabilizing	0.936	D	0.679	prob.neutral	N	0.509534032	None	None	I
K/P	0.9544	likely_pathogenic	0.9533	pathogenic	0.345	Stabilizing	0.975	D	0.764	deleterious	None	None	None	None	I
K/Q	0.1885	likely_benign	0.2093	benign	-0.151	Destabilizing	0.783	D	0.712	prob.delet.	N	0.471842435	None	None	I
K/R	0.0888	likely_benign	0.0874	benign	-0.353	Destabilizing	0.436	N	0.556	neutral	N	0.46582054	None	None	I
K/S	0.5719	likely_pathogenic	0.6174	pathogenic	-0.528	Destabilizing	0.735	D	0.556	neutral	None	None	None	None	I
K/T	0.2124	likely_benign	0.2355	benign	-0.309	Destabilizing	0.004	N	0.336	neutral	N	0.385124741	None	None	I
K/V	0.4283	ambiguous	0.4556	ambiguous	0.345	Stabilizing	0.274	N	0.646	neutral	None	None	None	None	I
K/W	0.8088	likely_pathogenic	0.8363	pathogenic	-0.01	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
K/Y	0.7531	likely_pathogenic	0.7906	pathogenic	0.286	Stabilizing	0.848	D	0.777	deleterious	None	None	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.