TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8265	25018;25019;25020	chr2:178718213;178718212;178718211	chr2:179582940;179582939;179582938
N2AB	7948	24067;24068;24069	chr2:178718213;178718212;178718211	chr2:179582940;179582939;179582938
N2A	7021	21286;21287;21288	chr2:178718213;178718212;178718211	chr2:179582940;179582939;179582938
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-68
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4846
• 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
Y/N	None	None	0.997	N	0.552	0.306	0.554721145582	gnomAD-4.0.0	1.6283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89039E-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
Y/A	0.5959	likely_pathogenic	0.6185	pathogenic	-1.509	Destabilizing	0.985	D	0.507	neutral	None	None	None	None	N
Y/C	0.2251	likely_benign	0.2654	benign	-0.593	Destabilizing	1.0	D	0.547	neutral	N	0.503316512	None	None	N
Y/D	0.6137	likely_pathogenic	0.6754	pathogenic	0.054	Stabilizing	0.997	D	0.557	neutral	N	0.507814383	None	None	N
Y/E	0.7689	likely_pathogenic	0.7932	pathogenic	0.12	Stabilizing	0.985	D	0.529	neutral	None	None	None	None	N
Y/F	0.1179	likely_benign	0.108	benign	-0.492	Destabilizing	0.924	D	0.491	neutral	N	0.464063606	None	None	N
Y/G	0.66	likely_pathogenic	0.6875	pathogenic	-1.78	Destabilizing	0.993	D	0.546	neutral	None	None	None	None	N
Y/H	0.2258	likely_benign	0.2354	benign	-0.223	Destabilizing	0.997	D	0.517	neutral	N	0.473683167	None	None	N
Y/I	0.5216	ambiguous	0.5389	ambiguous	-0.725	Destabilizing	0.074	N	0.297	neutral	None	None	None	None	N
Y/K	0.6419	likely_pathogenic	0.6789	pathogenic	-0.686	Destabilizing	0.097	N	0.343	neutral	None	None	None	None	N
Y/L	0.593	likely_pathogenic	0.6235	pathogenic	-0.725	Destabilizing	0.347	N	0.455	neutral	None	None	None	None	N
Y/M	0.7435	likely_pathogenic	0.7538	pathogenic	-0.622	Destabilizing	0.993	D	0.505	neutral	None	None	None	None	N
Y/N	0.3341	likely_benign	0.3739	ambiguous	-1.108	Destabilizing	0.997	D	0.552	neutral	N	0.497040029	None	None	N
Y/P	0.9892	likely_pathogenic	0.9905	pathogenic	-0.976	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
Y/Q	0.5758	likely_pathogenic	0.6036	pathogenic	-0.966	Destabilizing	0.986	D	0.517	neutral	None	None	None	None	N
Y/R	0.3784	ambiguous	0.397	ambiguous	-0.37	Destabilizing	0.98	D	0.544	neutral	None	None	None	None	N
Y/S	0.263	likely_benign	0.2796	benign	-1.588	Destabilizing	0.962	D	0.521	neutral	N	0.45092095	None	None	N
Y/T	0.4627	ambiguous	0.4798	ambiguous	-1.428	Destabilizing	0.471	N	0.343	neutral	None	None	None	None	N
Y/V	0.3765	ambiguous	0.3817	ambiguous	-0.976	Destabilizing	0.932	D	0.469	neutral	None	None	None	None	N
Y/W	0.5529	ambiguous	0.5482	ambiguous	-0.263	Destabilizing	1.0	D	0.514	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.