TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21422	64489;64490;64491	chr2:178586637;178586636;178586635	chr2:179451364;179451363;179451362
N2AB	19781	59566;59567;59568	chr2:178586637;178586636;178586635	chr2:179451364;179451363;179451362
N2A	18854	56785;56786;56787	chr2:178586637;178586636;178586635	chr2:179451364;179451363;179451362
N2B	12357	37294;37295;37296	chr2:178586637;178586636;178586635	chr2:179451364;179451363;179451362
Novex-1	12482	37669;37670;37671	chr2:178586637;178586636;178586635	chr2:179451364;179451363;179451362
Novex-2	12549	37870;37871;37872	chr2:178586637;178586636;178586635	chr2:179451364;179451363;179451362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-43
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7077
• 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
K/N	rs758963173	None	1.0	N	0.782	0.259	0.258779203287	gnomAD-4.0.0	4.10669E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39842E-06	0	0
K/R	None	None	0.999	N	0.631	0.303	0.410071178582	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.767	likely_pathogenic	0.6922	pathogenic	-0.038	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/C	0.9259	likely_pathogenic	0.9062	pathogenic	-0.32	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/D	0.8373	likely_pathogenic	0.7797	pathogenic	0.069	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/E	0.5578	ambiguous	0.4567	ambiguous	0.105	Stabilizing	0.999	D	0.681	prob.neutral	N	0.475786817	None	None	N
K/F	0.981	likely_pathogenic	0.9708	pathogenic	-0.091	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
K/G	0.7301	likely_pathogenic	0.6783	pathogenic	-0.275	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/H	0.6055	likely_pathogenic	0.5545	ambiguous	-0.466	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/I	0.9226	likely_pathogenic	0.8846	pathogenic	0.52	Stabilizing	1.0	D	0.753	deleterious	N	0.483107165	None	None	N
K/L	0.8427	likely_pathogenic	0.7909	pathogenic	0.52	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/M	0.757	likely_pathogenic	0.673	pathogenic	0.148	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/N	0.7647	likely_pathogenic	0.7029	pathogenic	0.035	Stabilizing	1.0	D	0.782	deleterious	N	0.477941688	None	None	N
K/P	0.7648	likely_pathogenic	0.695	pathogenic	0.363	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/Q	0.3662	ambiguous	0.3109	benign	-0.07	Destabilizing	1.0	D	0.761	deleterious	N	0.510939541	None	None	N
K/R	0.1071	likely_benign	0.1046	benign	-0.145	Destabilizing	0.999	D	0.631	neutral	N	0.478536334	None	None	N
K/S	0.756	likely_pathogenic	0.6934	pathogenic	-0.45	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
K/T	0.548	ambiguous	0.4704	ambiguous	-0.252	Destabilizing	1.0	D	0.735	prob.delet.	N	0.485697167	None	None	N
K/V	0.8733	likely_pathogenic	0.8252	pathogenic	0.363	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
K/W	0.9415	likely_pathogenic	0.9202	pathogenic	-0.108	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/Y	0.9338	likely_pathogenic	0.9102	pathogenic	0.224	Stabilizing	1.0	D	0.725	prob.delet.	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.