TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19112	57559;57560;57561	chr2:178597748;178597747;178597746	chr2:179462475;179462474;179462473
N2AB	17471	52636;52637;52638	chr2:178597748;178597747;178597746	chr2:179462475;179462474;179462473
N2A	16544	49855;49856;49857	chr2:178597748;178597747;178597746	chr2:179462475;179462474;179462473
N2B	10047	30364;30365;30366	chr2:178597748;178597747;178597746	chr2:179462475;179462474;179462473
Novex-1	10172	30739;30740;30741	chr2:178597748;178597747;178597746	chr2:179462475;179462474;179462473
Novex-2	10239	30940;30941;30942	chr2:178597748;178597747;178597746	chr2:179462475;179462474;179462473
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-117
• Domain position: 18
• Structural Position: 30
• Q(SASA): 0.1641
• 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/T	None	None	1.0	D	0.828	0.584	0.865381639045	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.9798	likely_pathogenic	0.985	pathogenic	-2.473	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
I/C	0.9766	likely_pathogenic	0.9811	pathogenic	-1.646	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
I/D	0.9992	likely_pathogenic	0.9995	pathogenic	-2.852	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
I/E	0.9979	likely_pathogenic	0.9985	pathogenic	-2.602	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
I/F	0.6944	likely_pathogenic	0.7356	pathogenic	-1.595	Destabilizing	1.0	D	0.792	deleterious	N	0.484619731	None	None	N
I/G	0.9961	likely_pathogenic	0.9973	pathogenic	-2.984	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
I/H	0.9961	likely_pathogenic	0.9971	pathogenic	-2.259	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/K	0.9938	likely_pathogenic	0.9957	pathogenic	-1.925	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
I/L	0.1862	likely_benign	0.1932	benign	-0.975	Destabilizing	0.993	D	0.406	neutral	N	0.46293495	None	None	N
I/M	0.2776	likely_benign	0.3242	benign	-0.878	Destabilizing	1.0	D	0.737	prob.delet.	D	0.536059777	None	None	N
I/N	0.9878	likely_pathogenic	0.9922	pathogenic	-2.403	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.525993124	None	None	N
I/P	0.9978	likely_pathogenic	0.9986	pathogenic	-1.46	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
I/Q	0.9952	likely_pathogenic	0.9961	pathogenic	-2.231	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
I/R	0.9932	likely_pathogenic	0.9947	pathogenic	-1.73	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
I/S	0.9916	likely_pathogenic	0.9943	pathogenic	-3.034	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.525993124	None	None	N
I/T	0.9904	likely_pathogenic	0.9934	pathogenic	-2.63	Highly Destabilizing	1.0	D	0.828	deleterious	D	0.525739635	None	None	N
I/V	0.2268	likely_benign	0.2683	benign	-1.46	Destabilizing	0.993	D	0.381	neutral	D	0.533904906	None	None	N
I/W	0.9928	likely_pathogenic	0.9952	pathogenic	-1.871	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/Y	0.9733	likely_pathogenic	0.9815	pathogenic	-1.588	Destabilizing	1.0	D	0.823	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.