TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3269	10030;10031;10032	chr2:178764710;178764709;178764708	chr2:179629437;179629436;179629435
N2AB	3269	10030;10031;10032	chr2:178764710;178764709;178764708	chr2:179629437;179629436;179629435
N2A	3269	10030;10031;10032	chr2:178764710;178764709;178764708	chr2:179629437;179629436;179629435
N2B	3223	9892;9893;9894	chr2:178764710;178764709;178764708	chr2:179629437;179629436;179629435
Novex-1	3223	9892;9893;9894	chr2:178764710;178764709;178764708	chr2:179629437;179629436;179629435
Novex-2	3223	9892;9893;9894	chr2:178764710;178764709;178764708	chr2:179629437;179629436;179629435
Novex-3	3269	10030;10031;10032	chr2:178764710;178764709;178764708	chr2:179629437;179629436;179629435

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-23
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.8057
• 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
K/T	None	None	0.134	N	0.297	0.414	0.299427821978	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
K/A	0.3157	likely_benign	0.4882	ambiguous	-0.02	Destabilizing	0.863	D	0.507	neutral	None	None	None	None	I
K/C	0.7675	likely_pathogenic	0.8594	pathogenic	-0.232	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	I
K/D	0.5847	likely_pathogenic	0.7575	pathogenic	0.077	Stabilizing	0.939	D	0.573	neutral	None	None	None	None	I
K/E	0.1538	likely_benign	0.2983	benign	0.112	Stabilizing	0.704	D	0.527	neutral	N	0.472927397	None	None	I
K/F	0.8187	likely_pathogenic	0.9197	pathogenic	-0.06	Destabilizing	0.997	D	0.591	neutral	None	None	None	None	I
K/G	0.5141	ambiguous	0.7287	pathogenic	-0.266	Destabilizing	0.969	D	0.574	neutral	None	None	None	None	I
K/H	0.3299	likely_benign	0.4189	ambiguous	-0.515	Destabilizing	0.991	D	0.578	neutral	None	None	None	None	I
K/I	0.359	ambiguous	0.5247	ambiguous	0.562	Stabilizing	0.976	D	0.593	neutral	N	0.513375193	None	None	I
K/L	0.391	ambiguous	0.5743	pathogenic	0.562	Stabilizing	0.939	D	0.575	neutral	None	None	None	None	I
K/M	0.2756	likely_benign	0.4391	ambiguous	0.229	Stabilizing	0.997	D	0.581	neutral	None	None	None	None	I
K/N	0.4076	ambiguous	0.6031	pathogenic	0.115	Stabilizing	0.959	D	0.552	neutral	N	0.510387553	None	None	I
K/P	0.8888	likely_pathogenic	0.9527	pathogenic	0.398	Stabilizing	0.997	D	0.578	neutral	None	None	None	None	I
K/Q	0.1221	likely_benign	0.1657	benign	-0.004	Destabilizing	0.31	N	0.202	neutral	N	0.458613044	None	None	I
K/R	0.0814	likely_benign	0.0897	benign	-0.142	Destabilizing	0.92	D	0.538	neutral	N	0.506730513	None	None	I
K/S	0.3915	ambiguous	0.5552	ambiguous	-0.374	Destabilizing	0.759	D	0.515	neutral	None	None	None	None	I
K/T	0.181	likely_benign	0.2783	benign	-0.176	Destabilizing	0.134	N	0.297	neutral	N	0.486376786	None	None	I
K/V	0.2916	likely_benign	0.4181	ambiguous	0.398	Stabilizing	0.939	D	0.599	neutral	None	None	None	None	I
K/W	0.8343	likely_pathogenic	0.915	pathogenic	-0.067	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	I
K/Y	0.6869	likely_pathogenic	0.8376	pathogenic	0.265	Stabilizing	0.997	D	0.621	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.