TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9620	29083;29084;29085	chr2:178707709;178707708;178707707	chr2:179572436;179572435;179572434
N2AB	9303	28132;28133;28134	chr2:178707709;178707708;178707707	chr2:179572436;179572435;179572434
N2A	8376	25351;25352;25353	chr2:178707709;178707708;178707707	chr2:179572436;179572435;179572434
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-82
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.5706
• 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
R/K	None	None	0.028	None	0.147	0.126	0.223847106136	gnomAD-4.0.0	1.59104E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85783E-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
R/A	0.6023	likely_pathogenic	0.3763	ambiguous	-0.137	Destabilizing	0.737	D	0.36	neutral	None	None	None	None	I
R/C	0.3842	ambiguous	0.2229	benign	-0.327	Destabilizing	0.998	D	0.423	neutral	None	None	None	None	I
R/D	0.8477	likely_pathogenic	0.6723	pathogenic	-0.073	Destabilizing	0.872	D	0.495	neutral	None	None	None	None	I
R/E	0.5807	likely_pathogenic	0.3758	ambiguous	-0.013	Destabilizing	0.584	D	0.39	neutral	None	None	None	None	I
R/F	0.7385	likely_pathogenic	0.5809	pathogenic	-0.374	Destabilizing	0.98	D	0.448	neutral	None	None	None	None	I
R/G	0.4785	ambiguous	0.2658	benign	-0.325	Destabilizing	0.912	D	0.456	neutral	None	None	None	None	I
R/H	0.143	likely_benign	0.1041	benign	-0.723	Destabilizing	0.98	D	0.488	neutral	None	None	None	None	I
R/I	0.4226	ambiguous	0.2738	benign	0.321	Stabilizing	0.083	N	0.335	neutral	None	None	None	None	I
R/K	0.1326	likely_benign	0.1042	benign	-0.213	Destabilizing	0.028	N	0.147	neutral	None	None	None	None	I
R/L	0.405	ambiguous	0.2658	benign	0.321	Stabilizing	0.584	D	0.371	neutral	None	None	None	None	I
R/M	0.4546	ambiguous	0.2955	benign	-0.061	Destabilizing	0.973	D	0.466	neutral	None	None	None	None	I
R/N	0.7437	likely_pathogenic	0.535	ambiguous	0.015	Stabilizing	0.932	D	0.427	neutral	None	None	None	None	I
R/P	0.9437	likely_pathogenic	0.8512	pathogenic	0.188	Stabilizing	0.977	D	0.527	neutral	None	None	None	None	I
R/Q	0.1545	likely_benign	0.1049	benign	-0.108	Destabilizing	0.209	N	0.215	neutral	None	None	None	None	I
R/S	0.6457	likely_pathogenic	0.4141	ambiguous	-0.394	Destabilizing	0.514	D	0.428	neutral	None	None	None	None	I
R/T	0.3461	ambiguous	0.193	benign	-0.201	Destabilizing	0.064	N	0.239	neutral	None	None	None	None	I
R/V	0.5081	ambiguous	0.3383	benign	0.188	Stabilizing	0.584	D	0.407	neutral	None	None	None	None	I
R/W	0.3176	likely_benign	0.2052	benign	-0.394	Destabilizing	0.998	D	0.433	neutral	None	None	None	None	I
R/Y	0.6132	likely_pathogenic	0.4576	ambiguous	0.007	Stabilizing	0.993	D	0.455	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.