TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17707	53344;53345;53346	chr2:178607569;178607568;178607567	chr2:179472296;179472295;179472294
N2AB	16066	48421;48422;48423	chr2:178607569;178607568;178607567	chr2:179472296;179472295;179472294
N2A	15139	45640;45641;45642	chr2:178607569;178607568;178607567	chr2:179472296;179472295;179472294
N2B	8642	26149;26150;26151	chr2:178607569;178607568;178607567	chr2:179472296;179472295;179472294
Novex-1	8767	26524;26525;26526	chr2:178607569;178607568;178607567	chr2:179472296;179472295;179472294
Novex-2	8834	26725;26726;26727	chr2:178607569;178607568;178607567	chr2:179472296;179472295;179472294
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-113
• Domain position: 31
• Structural Position: 49
• Q(SASA): 0.157
• 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/A	None	None	0.034	N	0.317	0.072	0.0762999501168	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41546E-04	0	0	0
T/N	rs2055199446	None	0.901	N	0.621	0.157	0.222439326576	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/N	rs2055199446	None	0.901	N	0.621	0.157	0.222439326576	gnomAD-4.0.0	6.58874E-06	None	None	None	None	N	None	0	6.56168E-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
T/A	0.1187	likely_benign	0.0998	benign	-0.972	Destabilizing	0.034	N	0.317	neutral	N	0.483221717	None	None	N
T/C	0.4648	ambiguous	0.4464	ambiguous	-0.438	Destabilizing	0.996	D	0.68	prob.neutral	None	None	None	None	N
T/D	0.4799	ambiguous	0.4576	ambiguous	-0.122	Destabilizing	0.923	D	0.685	prob.neutral	None	None	None	None	N
T/E	0.2747	likely_benign	0.2544	benign	0.018	Stabilizing	0.633	D	0.645	neutral	None	None	None	None	N
T/F	0.32	likely_benign	0.303	benign	-0.834	Destabilizing	0.987	D	0.729	prob.delet.	None	None	None	None	N
T/G	0.2668	likely_benign	0.2474	benign	-1.344	Destabilizing	0.633	D	0.643	neutral	None	None	None	None	N
T/H	0.2766	likely_benign	0.2627	benign	-1.437	Destabilizing	0.989	D	0.711	prob.delet.	None	None	None	None	N
T/I	0.2781	likely_benign	0.243	benign	-0.023	Destabilizing	0.949	D	0.714	prob.delet.	N	0.496438943	None	None	N
T/K	0.182	likely_benign	0.1678	benign	-0.081	Destabilizing	0.011	N	0.426	neutral	None	None	None	None	N
T/L	0.1372	likely_benign	0.1177	benign	-0.023	Destabilizing	0.775	D	0.603	neutral	None	None	None	None	N
T/M	0.0994	likely_benign	0.0937	benign	-0.01	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	N
T/N	0.1656	likely_benign	0.1555	benign	-0.474	Destabilizing	0.901	D	0.621	neutral	N	0.465656068	None	None	N
T/P	0.8067	likely_pathogenic	0.8197	pathogenic	-0.306	Destabilizing	0.949	D	0.712	prob.delet.	N	0.488622168	None	None	N
T/Q	0.18	likely_benign	0.174	benign	-0.357	Destabilizing	0.858	D	0.72	prob.delet.	None	None	None	None	N
T/R	0.1659	likely_benign	0.1529	benign	-0.232	Destabilizing	0.858	D	0.693	prob.neutral	None	None	None	None	N
T/S	0.1293	likely_benign	0.1144	benign	-0.87	Destabilizing	0.034	N	0.434	neutral	N	0.430080665	None	None	N
T/V	0.2031	likely_benign	0.1751	benign	-0.306	Destabilizing	0.775	D	0.561	neutral	None	None	None	None	N
T/W	0.615	likely_pathogenic	0.6129	pathogenic	-0.829	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
T/Y	0.3467	ambiguous	0.3401	ambiguous	-0.485	Destabilizing	0.987	D	0.731	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.