TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30440	91543;91544;91545	chr2:178551213;178551212;178551211	chr2:179415940;179415939;179415938
N2AB	28799	86620;86621;86622	chr2:178551213;178551212;178551211	chr2:179415940;179415939;179415938
N2A	27872	83839;83840;83841	chr2:178551213;178551212;178551211	chr2:179415940;179415939;179415938
N2B	21375	64348;64349;64350	chr2:178551213;178551212;178551211	chr2:179415940;179415939;179415938
Novex-1	21500	64723;64724;64725	chr2:178551213;178551212;178551211	chr2:179415940;179415939;179415938
Novex-2	21567	64924;64925;64926	chr2:178551213;178551212;178551211	chr2:179415940;179415939;179415938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-110
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1622
• 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/I	rs1446052860	0.011	1.0	N	0.709	0.437	0.478905595755	gnomAD-4.0.0	1.36871E-06	None	None	None	None	N	None	0	0	None	0	5.0421E-05	None	0	0	0	0	0
T/P	None	None	1.0	N	0.722	0.547	0.500363902356	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0248E-05

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	0.2604	likely_benign	0.2311	benign	-1.058	Destabilizing	0.999	D	0.535	neutral	N	0.51971374	None	None	N
T/C	0.6491	likely_pathogenic	0.6226	pathogenic	-0.903	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
T/D	0.8719	likely_pathogenic	0.8606	pathogenic	-1.316	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
T/E	0.8309	likely_pathogenic	0.8161	pathogenic	-1.198	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/F	0.6378	likely_pathogenic	0.6055	pathogenic	-0.794	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/G	0.6075	likely_pathogenic	0.6276	pathogenic	-1.415	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
T/H	0.5323	ambiguous	0.5238	ambiguous	-1.59	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/I	0.51	ambiguous	0.485	ambiguous	-0.156	Destabilizing	1.0	D	0.709	prob.delet.	N	0.511536974	None	None	N
T/K	0.647	likely_pathogenic	0.6358	pathogenic	-0.819	Destabilizing	1.0	D	0.706	prob.neutral	N	0.508574026	None	None	N
T/L	0.3228	likely_benign	0.2909	benign	-0.156	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
T/M	0.1948	likely_benign	0.1812	benign	-0.044	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
T/N	0.4299	ambiguous	0.3964	ambiguous	-1.212	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
T/P	0.9372	likely_pathogenic	0.9424	pathogenic	-0.424	Destabilizing	1.0	D	0.722	prob.delet.	N	0.501909436	None	None	N
T/Q	0.5554	ambiguous	0.5368	ambiguous	-1.207	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/R	0.5881	likely_pathogenic	0.5821	pathogenic	-0.774	Destabilizing	1.0	D	0.732	prob.delet.	N	0.468041103	None	None	N
T/S	0.1898	likely_benign	0.1892	benign	-1.427	Destabilizing	0.999	D	0.528	neutral	N	0.443175754	None	None	N
T/V	0.3521	ambiguous	0.3291	benign	-0.424	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	N
T/W	0.8804	likely_pathogenic	0.8743	pathogenic	-0.841	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/Y	0.6672	likely_pathogenic	0.6332	pathogenic	-0.531	Destabilizing	1.0	D	0.779	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.