TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3960	12103;12104;12105	chr2:178741355;178741354;178741353	chr2:179606082;179606081;179606080
N2AB	3643	11152;11153;11154	chr2:178741355;178741354;178741353	chr2:179606082;179606081;179606080
N2A	None	None	chr2:None	chr2:None
N2B	3597	11014;11015;11016	chr2:178741355;178741354;178741353	chr2:179606082;179606081;179606080
Novex-1	3722	11389;11390;11391	chr2:178741355;178741354;178741353	chr2:179606082;179606081;179606080
Novex-2	3789	11590;11591;11592	chr2:178741355;178741354;178741353	chr2:179606082;179606081;179606080
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-28
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.216
• Predicted PPI site: I

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/P	rs1487929859	-0.808	0.033	N	0.479	0.085	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/P	rs1487929859	-0.808	0.033	N	0.479	0.085	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/P	rs1487929859	-0.808	0.033	N	0.479	0.085	None	gnomAD-4.0.0	2.56189E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.39273E-06	0	2.84398E-05

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	0.0808	likely_benign	0.0779	benign	-1.213	Destabilizing	None	N	0.121	neutral	N	0.449077292	None	None	I
T/C	0.3635	ambiguous	0.3457	ambiguous	-0.741	Destabilizing	0.245	N	0.45	neutral	None	None	None	None	I
T/D	0.3055	likely_benign	0.2912	benign	-0.16	Destabilizing	0.009	N	0.411	neutral	None	None	None	None	I
T/E	0.1711	likely_benign	0.1656	benign	-0.047	Destabilizing	0.009	N	0.397	neutral	None	None	None	None	I
T/F	0.2156	likely_benign	0.2051	benign	-1.043	Destabilizing	0.022	N	0.536	neutral	None	None	None	None	I
T/G	0.2912	likely_benign	0.2679	benign	-1.556	Destabilizing	0.009	N	0.457	neutral	None	None	None	None	I
T/H	0.2006	likely_benign	0.1995	benign	-1.57	Destabilizing	0.245	N	0.514	neutral	None	None	None	None	I
T/I	0.1204	likely_benign	0.115	benign	-0.35	Destabilizing	None	N	0.173	neutral	N	0.44751765	None	None	I
T/K	0.1195	likely_benign	0.1172	benign	-0.368	Destabilizing	None	N	0.171	neutral	N	0.41996323	None	None	I
T/L	0.0831	likely_benign	0.0851	benign	-0.35	Destabilizing	None	N	0.173	neutral	None	None	None	None	I
T/M	0.0754	likely_benign	0.0757	benign	-0.254	Destabilizing	0.001	N	0.335	neutral	None	None	None	None	I
T/N	0.1298	likely_benign	0.1264	benign	-0.625	Destabilizing	0.009	N	0.339	neutral	None	None	None	None	I
T/P	0.3797	ambiguous	0.3634	ambiguous	-0.607	Destabilizing	0.033	N	0.479	neutral	N	0.503968825	None	None	I
T/Q	0.1528	likely_benign	0.1584	benign	-0.616	Destabilizing	None	N	0.163	neutral	None	None	None	None	I
T/R	0.0847	likely_benign	0.0855	benign	-0.37	Destabilizing	None	N	0.194	neutral	N	0.445633024	None	None	I
T/S	0.1218	likely_benign	0.1178	benign	-1.076	Destabilizing	None	N	0.155	neutral	N	0.445633024	None	None	I
T/V	0.1077	likely_benign	0.105	benign	-0.607	Destabilizing	None	N	0.171	neutral	None	None	None	None	I
T/W	0.4778	ambiguous	0.4549	ambiguous	-0.936	Destabilizing	0.788	D	0.503	neutral	None	None	None	None	I
T/Y	0.248	likely_benign	0.2379	benign	-0.663	Destabilizing	0.085	N	0.553	neutral	None	None	None	None	I

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.