TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2216	6871;6872;6873	chr2:178775065;178775064;178775063	chr2:179639792;179639791;179639790
N2AB	2216	6871;6872;6873	chr2:178775065;178775064;178775063	chr2:179639792;179639791;179639790
N2A	2216	6871;6872;6873	chr2:178775065;178775064;178775063	chr2:179639792;179639791;179639790
N2B	2170	6733;6734;6735	chr2:178775065;178775064;178775063	chr2:179639792;179639791;179639790
Novex-1	2170	6733;6734;6735	chr2:178775065;178775064;178775063	chr2:179639792;179639791;179639790
Novex-2	2170	6733;6734;6735	chr2:178775065;178775064;178775063	chr2:179639792;179639791;179639790
Novex-3	2216	6871;6872;6873	chr2:178775065;178775064;178775063	chr2:179639792;179639791;179639790

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-11
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.3946
• 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
E/D	None	None	0.003	N	0.133	0.167	0.0666544352282	gnomAD-4.0.0	1.59077E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	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
E/A	0.0479	likely_benign	0.0469	benign	-0.313	Destabilizing	None	N	0.071	neutral	N	0.434125916	None	None	N
E/C	0.3437	ambiguous	0.3402	ambiguous	-0.183	Destabilizing	0.245	N	0.385	neutral	None	None	None	None	N
E/D	0.1077	likely_benign	0.1099	benign	-0.325	Destabilizing	0.003	N	0.133	neutral	N	0.47794347	None	None	N
E/F	0.4105	ambiguous	0.4094	ambiguous	-0.105	Destabilizing	0.085	N	0.46	neutral	None	None	None	None	N
E/G	0.0729	likely_benign	0.0717	benign	-0.51	Destabilizing	None	N	0.085	neutral	N	0.511920377	None	None	N
E/H	0.2107	likely_benign	0.2179	benign	0.281	Stabilizing	0.245	N	0.191	neutral	None	None	None	None	N
E/I	0.1532	likely_benign	0.1496	benign	0.173	Stabilizing	0.022	N	0.418	neutral	None	None	None	None	N
E/K	0.1275	likely_benign	0.1358	benign	0.308	Stabilizing	0.003	N	0.145	neutral	N	0.487725552	None	None	N
E/L	0.1525	likely_benign	0.1504	benign	0.173	Stabilizing	0.004	N	0.289	neutral	None	None	None	None	N
E/M	0.1796	likely_benign	0.1749	benign	0.113	Stabilizing	0.245	N	0.371	neutral	None	None	None	None	N
E/N	0.1231	likely_benign	0.1208	benign	-0.077	Destabilizing	0.009	N	0.149	neutral	None	None	None	None	N
E/P	0.1085	likely_benign	0.105	benign	0.031	Stabilizing	None	N	0.087	neutral	None	None	None	None	N
E/Q	0.0919	likely_benign	0.0932	benign	-0.028	Destabilizing	0.014	N	0.202	neutral	N	0.496956759	None	None	N
E/R	0.1692	likely_benign	0.1824	benign	0.604	Stabilizing	0.018	N	0.166	neutral	None	None	None	None	N
E/S	0.054	likely_benign	0.052	benign	-0.235	Destabilizing	None	N	0.065	neutral	None	None	None	None	N
E/T	0.0632	likely_benign	0.0608	benign	-0.068	Destabilizing	None	N	0.069	neutral	None	None	None	None	N
E/V	0.1078	likely_benign	0.1066	benign	0.031	Stabilizing	0.003	N	0.233	neutral	N	0.503397232	None	None	N
E/W	0.6093	likely_pathogenic	0.6243	pathogenic	0.06	Stabilizing	0.788	D	0.364	neutral	None	None	None	None	N
E/Y	0.2818	likely_benign	0.2894	benign	0.144	Stabilizing	0.085	N	0.435	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.