TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19082	57469;57470;57471	chr2:178597926;178597925;178597924	chr2:179462653;179462652;179462651
N2AB	17441	52546;52547;52548	chr2:178597926;178597925;178597924	chr2:179462653;179462652;179462651
N2A	16514	49765;49766;49767	chr2:178597926;178597925;178597924	chr2:179462653;179462652;179462651
N2B	10017	30274;30275;30276	chr2:178597926;178597925;178597924	chr2:179462653;179462652;179462651
Novex-1	10142	30649;30650;30651	chr2:178597926;178597925;178597924	chr2:179462653;179462652;179462651
Novex-2	10209	30850;30851;30852	chr2:178597926;178597925;178597924	chr2:179462653;179462652;179462651
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-26
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3433
• 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
E/D	None	None	0.991	N	0.589	0.128	0.292062946507	gnomAD-4.0.0	1.59246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85986E-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
E/A	0.1768	likely_benign	0.19	benign	-0.669	Destabilizing	0.991	D	0.644	neutral	N	0.4800537	None	None	N
E/C	0.8316	likely_pathogenic	0.8487	pathogenic	-0.443	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/D	0.4226	ambiguous	0.469	ambiguous	-0.924	Destabilizing	0.991	D	0.589	neutral	N	0.517841297	None	None	N
E/F	0.8209	likely_pathogenic	0.866	pathogenic	0.183	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/G	0.3646	ambiguous	0.3873	ambiguous	-1.046	Destabilizing	0.999	D	0.677	prob.neutral	N	0.46957745	None	None	N
E/H	0.6045	likely_pathogenic	0.6478	pathogenic	0.178	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/I	0.3557	ambiguous	0.4035	ambiguous	0.365	Stabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
E/K	0.1792	likely_benign	0.1901	benign	-0.389	Destabilizing	0.983	D	0.653	prob.neutral	N	0.422314905	None	None	N
E/L	0.3876	ambiguous	0.4341	ambiguous	0.365	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
E/M	0.4274	ambiguous	0.4597	ambiguous	0.632	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/N	0.5043	ambiguous	0.5375	ambiguous	-1.063	Destabilizing	0.999	D	0.655	prob.neutral	None	None	None	None	N
E/P	0.4674	ambiguous	0.4716	ambiguous	0.042	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/Q	0.1327	likely_benign	0.1353	benign	-0.89	Destabilizing	0.911	D	0.383	neutral	N	0.465489679	None	None	N
E/R	0.3104	likely_benign	0.3405	ambiguous	0.047	Stabilizing	0.998	D	0.685	prob.delet.	None	None	None	None	N
E/S	0.341	ambiguous	0.3706	ambiguous	-1.348	Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
E/T	0.2652	likely_benign	0.3061	benign	-1.021	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
E/V	0.2112	likely_benign	0.2446	benign	0.042	Stabilizing	0.999	D	0.776	deleterious	N	0.433473261	None	None	N
E/W	0.947	likely_pathogenic	0.9651	pathogenic	0.512	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/Y	0.7546	likely_pathogenic	0.8075	pathogenic	0.468	Stabilizing	1.0	D	0.866	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.