TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7226	21901;21902;21903	chr2:178723424;178723423;178723422	chr2:179588151;179588150;179588149
N2AB	6909	20950;20951;20952	chr2:178723424;178723423;178723422	chr2:179588151;179588150;179588149
N2A	5982	18169;18170;18171	chr2:178723424;178723423;178723422	chr2:179588151;179588150;179588149
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-56
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4066
• 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/M	None	None	0.946	D	0.813	0.746	0.666365135816	gnomAD-4.0.0	6.8583E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00954E-07	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	0.6921	likely_pathogenic	0.7529	pathogenic	-1.848	Destabilizing	0.834	D	0.667	neutral	D	0.62223297	None	None	N
V/C	0.9326	likely_pathogenic	0.9467	pathogenic	-1.309	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
V/D	0.9831	likely_pathogenic	0.9883	pathogenic	-2.127	Highly Destabilizing	0.979	D	0.793	deleterious	None	None	None	None	N
V/E	0.9431	likely_pathogenic	0.96	pathogenic	-1.933	Destabilizing	0.973	D	0.787	deleterious	D	0.648376494	None	None	N
V/F	0.7364	likely_pathogenic	0.7726	pathogenic	-1.027	Destabilizing	0.959	D	0.793	deleterious	None	None	None	None	N
V/G	0.8134	likely_pathogenic	0.8632	pathogenic	-2.36	Highly Destabilizing	0.973	D	0.755	deleterious	D	0.648376494	None	None	N
V/H	0.984	likely_pathogenic	0.9876	pathogenic	-2.08	Highly Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
V/I	0.1026	likely_benign	0.0948	benign	-0.44	Destabilizing	0.02	N	0.559	neutral	None	None	None	None	N
V/K	0.9619	likely_pathogenic	0.9709	pathogenic	-1.495	Destabilizing	0.979	D	0.788	deleterious	None	None	None	None	N
V/L	0.513	ambiguous	0.5185	ambiguous	-0.44	Destabilizing	0.263	N	0.685	prob.neutral	D	0.620214927	None	None	N
V/M	0.5774	likely_pathogenic	0.6111	pathogenic	-0.494	Destabilizing	0.946	D	0.813	deleterious	D	0.631953525	None	None	N
V/N	0.9507	likely_pathogenic	0.9641	pathogenic	-1.709	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
V/P	0.9267	likely_pathogenic	0.9453	pathogenic	-0.881	Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	N
V/Q	0.9345	likely_pathogenic	0.9495	pathogenic	-1.578	Destabilizing	0.993	D	0.813	deleterious	None	None	None	None	N
V/R	0.9347	likely_pathogenic	0.9469	pathogenic	-1.33	Destabilizing	0.979	D	0.799	deleterious	None	None	None	None	N
V/S	0.8243	likely_pathogenic	0.8705	pathogenic	-2.346	Highly Destabilizing	0.979	D	0.759	deleterious	None	None	None	None	N
V/T	0.7382	likely_pathogenic	0.7947	pathogenic	-2.015	Highly Destabilizing	0.87	D	0.729	prob.delet.	None	None	None	None	N
V/W	0.9911	likely_pathogenic	0.9928	pathogenic	-1.514	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
V/Y	0.9697	likely_pathogenic	0.9728	pathogenic	-1.116	Destabilizing	0.979	D	0.803	deleterious	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.