TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30837	92734;92735;92736	chr2:178549117;178549116;178549115	chr2:179413844;179413843;179413842
N2AB	29196	87811;87812;87813	chr2:178549117;178549116;178549115	chr2:179413844;179413843;179413842
N2A	28269	85030;85031;85032	chr2:178549117;178549116;178549115	chr2:179413844;179413843;179413842
N2B	21772	65539;65540;65541	chr2:178549117;178549116;178549115	chr2:179413844;179413843;179413842
Novex-1	21897	65914;65915;65916	chr2:178549117;178549116;178549115	chr2:179413844;179413843;179413842
Novex-2	21964	66115;66116;66117	chr2:178549117;178549116;178549115	chr2:179413844;179413843;179413842
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-113
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.2037
• 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
T/S	None	None	0.014	N	0.187	0.068	0.104622674875	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
T/A	0.0957	likely_benign	0.0932	benign	-0.315	Destabilizing	0.349	N	0.429	neutral	N	0.517038794	None	None	N
T/C	0.4408	ambiguous	0.4352	ambiguous	-0.771	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
T/D	0.5755	likely_pathogenic	0.5524	ambiguous	-1.777	Destabilizing	0.775	D	0.651	neutral	None	None	None	None	N
T/E	0.5625	ambiguous	0.5633	ambiguous	-1.767	Destabilizing	0.775	D	0.645	neutral	None	None	None	None	N
T/F	0.4029	ambiguous	0.3921	ambiguous	-0.967	Destabilizing	0.961	D	0.777	deleterious	None	None	None	None	N
T/G	0.2773	likely_benign	0.2573	benign	-0.484	Destabilizing	0.633	D	0.621	neutral	None	None	None	None	N
T/H	0.3219	likely_benign	0.3143	benign	-1.025	Destabilizing	0.989	D	0.762	deleterious	None	None	None	None	N
T/I	0.5672	likely_pathogenic	0.5807	pathogenic	0.037	Stabilizing	0.949	D	0.712	prob.delet.	N	0.493262156	None	None	N
T/K	0.479	ambiguous	0.4882	ambiguous	-0.414	Destabilizing	0.633	D	0.647	neutral	None	None	None	None	N
T/L	0.2583	likely_benign	0.2558	benign	0.037	Stabilizing	0.775	D	0.608	neutral	None	None	None	None	N
T/M	0.1218	likely_benign	0.1259	benign	0.303	Stabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
T/N	0.208	likely_benign	0.1968	benign	-0.822	Destabilizing	0.565	D	0.539	neutral	N	0.51980974	None	None	N
T/P	0.9203	likely_pathogenic	0.9159	pathogenic	-0.052	Destabilizing	0.949	D	0.709	prob.delet.	N	0.504618461	None	None	N
T/Q	0.3828	ambiguous	0.3838	ambiguous	-1.153	Destabilizing	0.923	D	0.724	prob.delet.	None	None	None	None	N
T/R	0.3875	ambiguous	0.4052	ambiguous	-0.162	Destabilizing	0.923	D	0.72	prob.delet.	None	None	None	None	N
T/S	0.0826	likely_benign	0.0762	benign	-0.739	Destabilizing	0.014	N	0.187	neutral	N	0.365285399	None	None	N
T/V	0.3499	ambiguous	0.3564	ambiguous	-0.052	Destabilizing	0.775	D	0.513	neutral	None	None	None	None	N
T/W	0.7274	likely_pathogenic	0.7214	pathogenic	-1.103	Destabilizing	0.996	D	0.776	deleterious	None	None	None	None	N
T/Y	0.4095	ambiguous	0.3966	ambiguous	-0.632	Destabilizing	0.987	D	0.775	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.