TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22770	68533;68534;68535	chr2:178578632;178578631;178578630	chr2:179443359;179443358;179443357
N2AB	21129	63610;63611;63612	chr2:178578632;178578631;178578630	chr2:179443359;179443358;179443357
N2A	20202	60829;60830;60831	chr2:178578632;178578631;178578630	chr2:179443359;179443358;179443357
N2B	13705	41338;41339;41340	chr2:178578632;178578631;178578630	chr2:179443359;179443358;179443357
Novex-1	13830	41713;41714;41715	chr2:178578632;178578631;178578630	chr2:179443359;179443358;179443357
Novex-2	13897	41914;41915;41916	chr2:178578632;178578631;178578630	chr2:179443359;179443358;179443357
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: Fn3-53
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2814
• 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/I	rs2047000667	None	0.997	N	0.664	0.328	0.423119698836	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs2047000667	None	0.997	N	0.664	0.328	0.423119698836	gnomAD-4.0.0	1.86161E-06	None	None	None	None	I	None	1.33701E-05	0	None	0	0	None	0	0	1.69668E-06	0	0
T/S	None	None	0.659	N	0.246	0.125	0.181679512989	gnomAD-4.0.0	1.37035E-06	None	None	None	None	I	None	0	0	None	0	2.53588E-05	None	0	0	9.0025E-07	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	0.1584	likely_benign	0.158	benign	-0.944	Destabilizing	0.911	D	0.484	neutral	N	0.472343867	None	None	I
T/C	0.6472	likely_pathogenic	0.6499	pathogenic	-0.726	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
T/D	0.2414	likely_benign	0.3065	benign	-0.871	Destabilizing	0.171	N	0.306	neutral	None	None	None	None	I
T/E	0.4916	ambiguous	0.5022	ambiguous	-0.847	Destabilizing	0.971	D	0.533	neutral	None	None	None	None	I
T/F	0.6072	likely_pathogenic	0.5719	pathogenic	-1.06	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	I
T/G	0.3316	likely_benign	0.3136	benign	-1.214	Destabilizing	0.985	D	0.653	neutral	None	None	None	None	I
T/H	0.4216	ambiguous	0.4377	ambiguous	-1.582	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	I
T/I	0.5587	ambiguous	0.5295	ambiguous	-0.306	Destabilizing	0.997	D	0.664	neutral	N	0.47051707	None	None	I
T/K	0.4581	ambiguous	0.4742	ambiguous	-0.807	Destabilizing	0.985	D	0.586	neutral	None	None	None	None	I
T/L	0.253	likely_benign	0.2444	benign	-0.306	Destabilizing	0.993	D	0.593	neutral	None	None	None	None	I
T/M	0.1642	likely_benign	0.155	benign	0.048	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	I
T/N	0.0892	likely_benign	0.1103	benign	-0.903	Destabilizing	0.4	N	0.253	neutral	N	0.402483924	None	None	I
T/P	0.2309	likely_benign	0.2003	benign	-0.488	Destabilizing	0.999	D	0.656	neutral	N	0.464801819	None	None	I
T/Q	0.414	ambiguous	0.4232	ambiguous	-1.102	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	I
T/R	0.4198	ambiguous	0.4324	ambiguous	-0.598	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	I
T/S	0.1114	likely_benign	0.1205	benign	-1.12	Destabilizing	0.659	D	0.246	neutral	N	0.448330857	None	None	I
T/V	0.3888	ambiguous	0.3694	ambiguous	-0.488	Destabilizing	0.993	D	0.528	neutral	None	None	None	None	I
T/W	0.8132	likely_pathogenic	0.7993	pathogenic	-1.007	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
T/Y	0.4896	ambiguous	0.4831	ambiguous	-0.737	Destabilizing	0.999	D	0.741	deleterious	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.