TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3100	9523;9524;9525	chr2:178768021;178768020;178768019	chr2:179632748;179632747;179632746
N2AB	3100	9523;9524;9525	chr2:178768021;178768020;178768019	chr2:179632748;179632747;179632746
N2A	3100	9523;9524;9525	chr2:178768021;178768020;178768019	chr2:179632748;179632747;179632746
N2B	3054	9385;9386;9387	chr2:178768021;178768020;178768019	chr2:179632748;179632747;179632746
Novex-1	3054	9385;9386;9387	chr2:178768021;178768020;178768019	chr2:179632748;179632747;179632746
Novex-2	3054	9385;9386;9387	chr2:178768021;178768020;178768019	chr2:179632748;179632747;179632746
Novex-3	3100	9523;9524;9525	chr2:178768021;178768020;178768019	chr2:179632748;179632747;179632746

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-21
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.2779
• 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/I	rs780950679	0.089	None	N	0.203	0.039	0.0401082797425	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
T/I	rs780950679	0.089	None	N	0.203	0.039	0.0401082797425	gnomAD-4.0.0	3.1811E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85651E-06	1.43271E-05	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	0.0736	likely_benign	0.0712	benign	-0.21	Destabilizing	None	N	0.105	neutral	N	0.34079072	None	None	N
T/C	0.4157	ambiguous	0.3843	ambiguous	-0.363	Destabilizing	0.245	N	0.327	neutral	None	None	None	None	N
T/D	0.2568	likely_benign	0.2529	benign	0.298	Stabilizing	0.009	N	0.349	neutral	None	None	None	None	N
T/E	0.2395	likely_benign	0.2275	benign	0.241	Stabilizing	None	N	0.146	neutral	None	None	None	None	N
T/F	0.2235	likely_benign	0.2421	benign	-0.673	Destabilizing	0.044	N	0.502	neutral	None	None	None	None	N
T/G	0.1531	likely_benign	0.1477	benign	-0.352	Destabilizing	None	N	0.151	neutral	None	None	None	None	N
T/H	0.2619	likely_benign	0.2554	benign	-0.588	Destabilizing	0.245	N	0.409	neutral	None	None	None	None	N
T/I	0.1303	likely_benign	0.1403	benign	0.044	Stabilizing	None	N	0.203	neutral	N	0.34719777	None	None	N
T/K	0.2106	likely_benign	0.2246	benign	-0.314	Destabilizing	0.007	N	0.354	neutral	N	0.333970582	None	None	N
T/L	0.1036	likely_benign	0.1059	benign	0.044	Stabilizing	0.004	N	0.291	neutral	None	None	None	None	N
T/M	0.0891	likely_benign	0.0917	benign	-0.049	Destabilizing	0.138	N	0.339	neutral	None	None	None	None	N
T/N	0.0962	likely_benign	0.0985	benign	-0.21	Destabilizing	0.044	N	0.237	neutral	None	None	None	None	N
T/P	0.1485	likely_benign	0.16	benign	-0.011	Destabilizing	None	N	0.201	neutral	N	0.34034036	None	None	N
T/Q	0.2183	likely_benign	0.209	benign	-0.352	Destabilizing	0.022	N	0.419	neutral	None	None	None	None	N
T/R	0.1813	likely_benign	0.1988	benign	-0.09	Destabilizing	0.033	N	0.417	neutral	N	0.337957463	None	None	N
T/S	0.0874	likely_benign	0.0839	benign	-0.402	Destabilizing	0.001	N	0.143	neutral	N	0.292398468	None	None	N
T/V	0.0996	likely_benign	0.1029	benign	-0.011	Destabilizing	None	N	0.088	neutral	None	None	None	None	N
T/W	0.5708	likely_pathogenic	0.5663	pathogenic	-0.736	Destabilizing	0.788	D	0.398	neutral	None	None	None	None	N
T/Y	0.3269	likely_benign	0.3303	benign	-0.42	Destabilizing	0.245	N	0.496	neutral	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.