TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33132	99619;99620;99621	chr2:178537813;178537812;178537811	chr2:179402540;179402539;179402538
N2AB	31491	94696;94697;94698	chr2:178537813;178537812;178537811	chr2:179402540;179402539;179402538
N2A	30564	91915;91916;91917	chr2:178537813;178537812;178537811	chr2:179402540;179402539;179402538
N2B	24067	72424;72425;72426	chr2:178537813;178537812;178537811	chr2:179402540;179402539;179402538
Novex-1	24192	72799;72800;72801	chr2:178537813;178537812;178537811	chr2:179402540;179402539;179402538
Novex-2	24259	73000;73001;73002	chr2:178537813;178537812;178537811	chr2:179402540;179402539;179402538
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-156
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1815
• 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/L	rs780831102	-0.838	0.955	N	0.405	0.469	0.700996906393	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
I/L	rs780831102	-0.838	0.955	N	0.405	0.469	0.700996906393	gnomAD-4.0.0	5.47402E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19606E-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	0.9191	likely_pathogenic	0.945	pathogenic	-2.044	Highly Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
I/C	0.9393	likely_pathogenic	0.9536	pathogenic	-0.935	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
I/D	0.9975	likely_pathogenic	0.9977	pathogenic	-1.899	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
I/E	0.9912	likely_pathogenic	0.9916	pathogenic	-1.856	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/F	0.6542	likely_pathogenic	0.6525	pathogenic	-1.44	Destabilizing	1.0	D	0.765	deleterious	N	0.494248975	None	None	N
I/G	0.9902	likely_pathogenic	0.9924	pathogenic	-2.412	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/H	0.9881	likely_pathogenic	0.9894	pathogenic	-1.783	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
I/K	0.9775	likely_pathogenic	0.9751	pathogenic	-1.498	Destabilizing	0.998	D	0.858	deleterious	None	None	None	None	N
I/L	0.3586	ambiguous	0.3888	ambiguous	-1.061	Destabilizing	0.955	D	0.405	neutral	N	0.516132796	None	None	N
I/M	0.2984	likely_benign	0.3028	benign	-0.654	Destabilizing	0.999	D	0.725	prob.delet.	N	0.507442159	None	None	N
I/N	0.9562	likely_pathogenic	0.9566	pathogenic	-1.254	Destabilizing	1.0	D	0.867	deleterious	D	0.529180492	None	None	N
I/P	0.993	likely_pathogenic	0.9936	pathogenic	-1.362	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/Q	0.9817	likely_pathogenic	0.9823	pathogenic	-1.398	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/R	0.972	likely_pathogenic	0.9687	pathogenic	-0.922	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
I/S	0.9374	likely_pathogenic	0.9456	pathogenic	-1.788	Destabilizing	1.0	D	0.845	deleterious	D	0.535674952	None	None	N
I/T	0.8164	likely_pathogenic	0.8523	pathogenic	-1.635	Destabilizing	1.0	D	0.767	deleterious	N	0.507442159	None	None	N
I/V	0.1268	likely_benign	0.1401	benign	-1.362	Destabilizing	0.966	D	0.356	neutral	N	0.408393963	None	None	N
I/W	0.9903	likely_pathogenic	0.9905	pathogenic	-1.62	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/Y	0.9694	likely_pathogenic	0.9672	pathogenic	-1.42	Destabilizing	0.999	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.