TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25393	76402;76403;76404	chr2:178569955;178569954;178569953	chr2:179434682;179434681;179434680
N2AB	23752	71479;71480;71481	chr2:178569955;178569954;178569953	chr2:179434682;179434681;179434680
N2A	22825	68698;68699;68700	chr2:178569955;178569954;178569953	chr2:179434682;179434681;179434680
N2B	16328	49207;49208;49209	chr2:178569955;178569954;178569953	chr2:179434682;179434681;179434680
Novex-1	16453	49582;49583;49584	chr2:178569955;178569954;178569953	chr2:179434682;179434681;179434680
Novex-2	16520	49783;49784;49785	chr2:178569955;178569954;178569953	chr2:179434682;179434681;179434680
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-72
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.383
• 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
P/S	rs1005590673	None	0.18	N	0.372	0.164	0.165133752707	gnomAD-4.0.0	3.18885E-06	None	None	None	None	N	None	0	4.57917E-05	None	0	0	None	0	0	0	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
P/A	0.0486	likely_benign	0.0512	benign	-1.587	Destabilizing	0.087	N	0.344	neutral	N	0.470647569	None	None	N
P/C	0.2989	likely_benign	0.3226	benign	-0.921	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	N
P/D	0.7101	likely_pathogenic	0.6843	pathogenic	-1.4	Destabilizing	0.971	D	0.536	neutral	None	None	None	None	N
P/E	0.4049	ambiguous	0.3899	ambiguous	-1.391	Destabilizing	0.971	D	0.585	neutral	None	None	None	None	N
P/F	0.4879	ambiguous	0.4596	ambiguous	-1.27	Destabilizing	0.999	D	0.732	deleterious	None	None	None	None	N
P/G	0.3181	likely_benign	0.3191	benign	-1.91	Destabilizing	0.825	D	0.559	neutral	None	None	None	None	N
P/H	0.3052	likely_benign	0.2819	benign	-1.443	Destabilizing	0.998	D	0.667	prob.neutral	N	0.50310707	None	None	N
P/I	0.1819	likely_benign	0.1722	benign	-0.793	Destabilizing	0.985	D	0.746	deleterious	None	None	None	None	N
P/K	0.4008	ambiguous	0.4038	ambiguous	-1.142	Destabilizing	0.971	D	0.565	neutral	None	None	None	None	N
P/L	0.1253	likely_benign	0.116	benign	-0.793	Destabilizing	0.961	D	0.701	prob.delet.	N	0.475631064	None	None	N
P/M	0.2696	likely_benign	0.2768	benign	-0.56	Destabilizing	0.999	D	0.659	prob.neutral	None	None	None	None	N
P/N	0.4744	ambiguous	0.4604	ambiguous	-0.948	Destabilizing	0.971	D	0.686	prob.delet.	None	None	None	None	N
P/Q	0.2205	likely_benign	0.2137	benign	-1.13	Destabilizing	0.985	D	0.527	neutral	None	None	None	None	N
P/R	0.2859	likely_benign	0.2653	benign	-0.631	Destabilizing	0.961	D	0.686	prob.delet.	N	0.502346601	None	None	N
P/S	0.1195	likely_benign	0.1158	benign	-1.482	Destabilizing	0.18	N	0.372	neutral	N	0.506280296	None	None	N
P/T	0.0942	likely_benign	0.0921	benign	-1.367	Destabilizing	0.78	D	0.564	neutral	N	0.500815761	None	None	N
P/V	0.1151	likely_benign	0.1121	benign	-1.024	Destabilizing	0.971	D	0.637	neutral	None	None	None	None	N
P/W	0.7183	likely_pathogenic	0.7059	pathogenic	-1.47	Destabilizing	0.999	D	0.665	prob.neutral	None	None	None	None	N
P/Y	0.5191	ambiguous	0.5136	ambiguous	-1.167	Destabilizing	0.999	D	0.731	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.