TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26812	80659;80660;80661	chr2:178565698;178565697;178565696	chr2:179430425;179430424;179430423
N2AB	25171	75736;75737;75738	chr2:178565698;178565697;178565696	chr2:179430425;179430424;179430423
N2A	24244	72955;72956;72957	chr2:178565698;178565697;178565696	chr2:179430425;179430424;179430423
N2B	17747	53464;53465;53466	chr2:178565698;178565697;178565696	chr2:179430425;179430424;179430423
Novex-1	17872	53839;53840;53841	chr2:178565698;178565697;178565696	chr2:179430425;179430424;179430423
Novex-2	17939	54040;54041;54042	chr2:178565698;178565697;178565696	chr2:179430425;179430424;179430423
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-83
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.309
• 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
V/I	None	None	None	N	0.13	0.177	0.126345400529	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	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
V/A	0.8165	likely_pathogenic	0.7961	pathogenic	-1.847	Destabilizing	0.027	N	0.529	neutral	N	0.468074198	None	None	N
V/C	0.882	likely_pathogenic	0.872	pathogenic	-1.1	Destabilizing	0.935	D	0.654	neutral	None	None	None	None	N
V/D	0.9667	likely_pathogenic	0.9663	pathogenic	-2.152	Highly Destabilizing	0.317	N	0.727	prob.delet.	N	0.509843463	None	None	N
V/E	0.941	likely_pathogenic	0.939	pathogenic	-1.973	Destabilizing	0.38	N	0.705	prob.neutral	None	None	None	None	N
V/F	0.5969	likely_pathogenic	0.5594	ambiguous	-1.169	Destabilizing	0.317	N	0.697	prob.neutral	N	0.520020384	None	None	N
V/G	0.8294	likely_pathogenic	0.8329	pathogenic	-2.34	Highly Destabilizing	0.117	N	0.733	prob.delet.	N	0.488996195	None	None	N
V/H	0.9633	likely_pathogenic	0.962	pathogenic	-2.072	Highly Destabilizing	0.935	D	0.702	prob.neutral	None	None	None	None	N
V/I	0.0541	likely_benign	0.0506	benign	-0.494	Destabilizing	None	N	0.13	neutral	N	0.325191003	None	None	N
V/K	0.9592	likely_pathogenic	0.9581	pathogenic	-1.467	Destabilizing	0.38	N	0.704	prob.neutral	None	None	None	None	N
V/L	0.1747	likely_benign	0.174	benign	-0.494	Destabilizing	0.004	N	0.351	neutral	N	0.412834204	None	None	N
V/M	0.3548	ambiguous	0.3358	benign	-0.337	Destabilizing	0.38	N	0.649	neutral	None	None	None	None	N
V/N	0.7809	likely_pathogenic	0.7702	pathogenic	-1.641	Destabilizing	0.38	N	0.715	prob.delet.	None	None	None	None	N
V/P	0.7873	likely_pathogenic	0.7857	pathogenic	-0.916	Destabilizing	0.555	D	0.687	prob.neutral	None	None	None	None	N
V/Q	0.9297	likely_pathogenic	0.9294	pathogenic	-1.551	Destabilizing	0.555	D	0.697	prob.neutral	None	None	None	None	N
V/R	0.9417	likely_pathogenic	0.9404	pathogenic	-1.23	Destabilizing	0.38	N	0.727	prob.delet.	None	None	None	None	N
V/S	0.8484	likely_pathogenic	0.8268	pathogenic	-2.25	Highly Destabilizing	0.081	N	0.663	neutral	None	None	None	None	N
V/T	0.7893	likely_pathogenic	0.7648	pathogenic	-1.937	Destabilizing	0.001	N	0.23	neutral	None	None	None	None	N
V/W	0.9723	likely_pathogenic	0.9708	pathogenic	-1.672	Destabilizing	0.935	D	0.717	prob.delet.	None	None	None	None	N
V/Y	0.9115	likely_pathogenic	0.9041	pathogenic	-1.262	Destabilizing	0.555	D	0.677	prob.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.