TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23402	70429;70430;70431	chr2:178575928;178575927;178575926	chr2:179440655;179440654;179440653
N2AB	21761	65506;65507;65508	chr2:178575928;178575927;178575926	chr2:179440655;179440654;179440653
N2A	20834	62725;62726;62727	chr2:178575928;178575927;178575926	chr2:179440655;179440654;179440653
N2B	14337	43234;43235;43236	chr2:178575928;178575927;178575926	chr2:179440655;179440654;179440653
Novex-1	14462	43609;43610;43611	chr2:178575928;178575927;178575926	chr2:179440655;179440654;179440653
Novex-2	14529	43810;43811;43812	chr2:178575928;178575927;178575926	chr2:179440655;179440654;179440653
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-129
• Domain position: 58
• Structural Position: 140
• Q(SASA): 0.1667
• 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	0.014	D	0.554	0.708	0.790246465493	gnomAD-4.0.0	2.73739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59868E-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	0.9608	likely_pathogenic	0.9721	pathogenic	-2.58	Highly Destabilizing	0.559	D	0.716	prob.delet.	None	None	None	None	N
I/C	0.9508	likely_pathogenic	0.9626	pathogenic	-1.991	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
I/D	0.996	likely_pathogenic	0.9968	pathogenic	-2.872	Highly Destabilizing	0.956	D	0.872	deleterious	None	None	None	None	N
I/E	0.9899	likely_pathogenic	0.9917	pathogenic	-2.727	Highly Destabilizing	0.956	D	0.865	deleterious	None	None	None	None	N
I/F	0.5453	ambiguous	0.6007	pathogenic	-1.686	Destabilizing	0.97	D	0.729	prob.delet.	D	0.582704258	None	None	N
I/G	0.9944	likely_pathogenic	0.9961	pathogenic	-3.063	Highly Destabilizing	0.956	D	0.851	deleterious	None	None	None	None	N
I/H	0.9756	likely_pathogenic	0.9806	pathogenic	-2.418	Highly Destabilizing	0.998	D	0.866	deleterious	None	None	None	None	N
I/K	0.9796	likely_pathogenic	0.9833	pathogenic	-2.112	Highly Destabilizing	0.956	D	0.863	deleterious	None	None	None	None	N
I/L	0.202	likely_benign	0.2306	benign	-1.219	Destabilizing	0.294	N	0.519	neutral	D	0.534405087	None	None	N
I/M	0.3075	likely_benign	0.369	ambiguous	-1.093	Destabilizing	0.97	D	0.689	prob.neutral	D	0.575567875	None	None	N
I/N	0.9404	likely_pathogenic	0.9544	pathogenic	-2.278	Highly Destabilizing	0.942	D	0.873	deleterious	D	0.583713279	None	None	N
I/P	0.9954	likely_pathogenic	0.9957	pathogenic	-1.65	Destabilizing	0.978	D	0.872	deleterious	None	None	None	None	N
I/Q	0.9742	likely_pathogenic	0.9793	pathogenic	-2.284	Highly Destabilizing	0.978	D	0.867	deleterious	None	None	None	None	N
I/R	0.9704	likely_pathogenic	0.9753	pathogenic	-1.597	Destabilizing	0.956	D	0.871	deleterious	None	None	None	None	N
I/S	0.9424	likely_pathogenic	0.957	pathogenic	-2.946	Highly Destabilizing	0.698	D	0.834	deleterious	D	0.609251391	None	None	N
I/T	0.9358	likely_pathogenic	0.9536	pathogenic	-2.668	Highly Destabilizing	0.014	N	0.554	neutral	D	0.608847783	None	None	N
I/V	0.1593	likely_benign	0.1918	benign	-1.65	Destabilizing	0.006	N	0.281	neutral	D	0.540198891	None	None	N
I/W	0.9815	likely_pathogenic	0.9847	pathogenic	-2.007	Highly Destabilizing	0.998	D	0.861	deleterious	None	None	None	None	N
I/Y	0.9251	likely_pathogenic	0.9378	pathogenic	-1.76	Destabilizing	0.993	D	0.787	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.