TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18759	56500;56501;56502	chr2:178599626;178599625;178599624	chr2:179464353;179464352;179464351
N2AB	17118	51577;51578;51579	chr2:178599626;178599625;178599624	chr2:179464353;179464352;179464351
N2A	16191	48796;48797;48798	chr2:178599626;178599625;178599624	chr2:179464353;179464352;179464351
N2B	9694	29305;29306;29307	chr2:178599626;178599625;178599624	chr2:179464353;179464352;179464351
Novex-1	9819	29680;29681;29682	chr2:178599626;178599625;178599624	chr2:179464353;179464352;179464351
Novex-2	9886	29881;29882;29883	chr2:178599626;178599625;178599624	chr2:179464353;179464352;179464351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-116
• Domain position: 72
• Structural Position: 151
• Q(SASA): 0.3604
• 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/P	None	None	0.994	N	0.655	0.584	0.46123363591	gnomAD-4.0.0	1.5952E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8642E-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
T/A	0.1803	likely_benign	0.1683	benign	-0.913	Destabilizing	0.835	D	0.413	neutral	N	0.442936185	None	None	N
T/C	0.63	likely_pathogenic	0.5634	ambiguous	-0.64	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
T/D	0.8382	likely_pathogenic	0.8392	pathogenic	-0.599	Destabilizing	0.97	D	0.561	neutral	None	None	None	None	N
T/E	0.7708	likely_pathogenic	0.7624	pathogenic	-0.583	Destabilizing	0.97	D	0.555	neutral	None	None	None	None	N
T/F	0.7368	likely_pathogenic	0.6843	pathogenic	-0.973	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
T/G	0.3392	likely_benign	0.3577	ambiguous	-1.184	Destabilizing	0.97	D	0.557	neutral	None	None	None	None	N
T/H	0.5732	likely_pathogenic	0.5692	pathogenic	-1.457	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/I	0.7767	likely_pathogenic	0.7018	pathogenic	-0.278	Destabilizing	0.994	D	0.653	neutral	D	0.528768445	None	None	N
T/K	0.5764	likely_pathogenic	0.5433	ambiguous	-0.79	Destabilizing	0.97	D	0.558	neutral	None	None	None	None	N
T/L	0.477	ambiguous	0.4062	ambiguous	-0.278	Destabilizing	0.985	D	0.539	neutral	None	None	None	None	N
T/M	0.2415	likely_benign	0.2106	benign	0.1	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
T/N	0.3793	ambiguous	0.3729	ambiguous	-0.818	Destabilizing	0.961	D	0.492	neutral	N	0.513260275	None	None	N
T/P	0.7417	likely_pathogenic	0.7269	pathogenic	-0.458	Destabilizing	0.994	D	0.655	neutral	N	0.494620006	None	None	N
T/Q	0.5471	ambiguous	0.5273	ambiguous	-1.02	Destabilizing	0.996	D	0.673	neutral	None	None	None	None	N
T/R	0.4258	ambiguous	0.3989	ambiguous	-0.536	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
T/S	0.1607	likely_benign	0.1623	benign	-1.094	Destabilizing	0.287	N	0.219	neutral	N	0.417461737	None	None	N
T/V	0.5691	likely_pathogenic	0.4886	ambiguous	-0.458	Destabilizing	0.985	D	0.483	neutral	None	None	None	None	N
T/W	0.916	likely_pathogenic	0.8894	pathogenic	-0.89	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/Y	0.7271	likely_pathogenic	0.679	pathogenic	-0.649	Destabilizing	0.999	D	0.718	prob.delet.	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.