TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33243	99952;99953;99954	chr2:178537480;178537479;178537478	chr2:179402207;179402206;179402205
N2AB	31602	95029;95030;95031	chr2:178537480;178537479;178537478	chr2:179402207;179402206;179402205
N2A	30675	92248;92249;92250	chr2:178537480;178537479;178537478	chr2:179402207;179402206;179402205
N2B	24178	72757;72758;72759	chr2:178537480;178537479;178537478	chr2:179402207;179402206;179402205
Novex-1	24303	73132;73133;73134	chr2:178537480;178537479;178537478	chr2:179402207;179402206;179402205
Novex-2	24370	73333;73334;73335	chr2:178537480;178537479;178537478	chr2:179402207;179402206;179402205
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-157
• Domain position: 41
• Structural Position: 121
• Q(SASA): 0.166
• 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
I/F	None	None	0.851	N	0.631	0.18	0.557129077062	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85876E-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
I/A	0.4553	ambiguous	0.5259	ambiguous	-2.353	Highly Destabilizing	0.03	N	0.341	neutral	None	None	None	None	N
I/C	0.6575	likely_pathogenic	0.7236	pathogenic	-1.656	Destabilizing	0.975	D	0.624	neutral	None	None	None	None	N
I/D	0.8863	likely_pathogenic	0.8801	pathogenic	-2.472	Highly Destabilizing	0.95	D	0.677	prob.neutral	None	None	None	None	N
I/E	0.7895	likely_pathogenic	0.7582	pathogenic	-2.417	Highly Destabilizing	0.8	D	0.636	neutral	None	None	None	None	N
I/F	0.2134	likely_benign	0.2585	benign	-1.745	Destabilizing	0.851	D	0.631	neutral	N	0.484900238	None	None	N
I/G	0.8274	likely_pathogenic	0.8694	pathogenic	-2.755	Highly Destabilizing	0.844	D	0.627	neutral	None	None	None	None	N
I/H	0.7218	likely_pathogenic	0.7349	pathogenic	-2.044	Highly Destabilizing	0.995	D	0.623	neutral	None	None	None	None	N
I/K	0.6626	likely_pathogenic	0.6598	pathogenic	-1.759	Destabilizing	0.138	N	0.641	neutral	None	None	None	None	N
I/L	0.1642	likely_benign	0.1811	benign	-1.257	Destabilizing	0.011	N	0.371	neutral	N	0.491460851	None	None	N
I/M	0.1232	likely_benign	0.1295	benign	-0.94	Destabilizing	0.632	D	0.623	neutral	N	0.508451888	None	None	N
I/N	0.4741	ambiguous	0.4662	ambiguous	-1.699	Destabilizing	0.935	D	0.655	neutral	N	0.490393725	None	None	N
I/P	0.9643	likely_pathogenic	0.9733	pathogenic	-1.597	Destabilizing	0.975	D	0.673	neutral	None	None	None	None	N
I/Q	0.6787	likely_pathogenic	0.6672	pathogenic	-1.853	Destabilizing	0.941	D	0.663	neutral	None	None	None	None	N
I/R	0.5536	ambiguous	0.5664	pathogenic	-1.14	Destabilizing	0.883	D	0.656	neutral	None	None	None	None	N
I/S	0.4746	ambiguous	0.5079	ambiguous	-2.318	Highly Destabilizing	0.672	D	0.591	neutral	N	0.516436653	None	None	N
I/T	0.2323	likely_benign	0.236	benign	-2.142	Highly Destabilizing	0.004	N	0.359	neutral	N	0.483497515	None	None	N
I/V	0.078	likely_benign	0.0872	benign	-1.597	Destabilizing	None	N	0.16	neutral	N	0.440127953	None	None	N
I/W	0.864	likely_pathogenic	0.8817	pathogenic	-1.933	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	N
I/Y	0.5826	likely_pathogenic	0.6134	pathogenic	-1.731	Destabilizing	0.643	D	0.665	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.