TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20302	61129;61130;61131	chr2:178590821;178590820;178590819	chr2:179455548;179455547;179455546
N2AB	18661	56206;56207;56208	chr2:178590821;178590820;178590819	chr2:179455548;179455547;179455546
N2A	17734	53425;53426;53427	chr2:178590821;178590820;178590819	chr2:179455548;179455547;179455546
N2B	11237	33934;33935;33936	chr2:178590821;178590820;178590819	chr2:179455548;179455547;179455546
Novex-1	11362	34309;34310;34311	chr2:178590821;178590820;178590819	chr2:179455548;179455547;179455546
Novex-2	11429	34510;34511;34512	chr2:178590821;178590820;178590819	chr2:179455548;179455547;179455546
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-35
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6241
• 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
P/L	None	None	0.497	N	0.605	0.373	0.56369308836	gnomAD-4.0.0	1.60886E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43658E-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
P/A	0.0816	likely_benign	0.0931	benign	-0.48	Destabilizing	0.22	N	0.534	neutral	N	0.510902255	None	None	I
P/C	0.4498	ambiguous	0.4997	ambiguous	-0.61	Destabilizing	0.968	D	0.722	prob.delet.	None	None	None	None	I
P/D	0.3914	ambiguous	0.4481	ambiguous	-0.166	Destabilizing	0.567	D	0.518	neutral	None	None	None	None	I
P/E	0.2278	likely_benign	0.2695	benign	-0.279	Destabilizing	0.157	N	0.527	neutral	None	None	None	None	I
P/F	0.4903	ambiguous	0.5662	pathogenic	-0.714	Destabilizing	0.909	D	0.691	prob.neutral	None	None	None	None	I
P/G	0.3718	ambiguous	0.4	ambiguous	-0.619	Destabilizing	0.272	N	0.561	neutral	None	None	None	None	I
P/H	0.1969	likely_benign	0.2258	benign	-0.207	Destabilizing	0.909	D	0.67	neutral	None	None	None	None	I
P/I	0.2609	likely_benign	0.306	benign	-0.269	Destabilizing	0.726	D	0.725	prob.delet.	None	None	None	None	I
P/K	0.229	likely_benign	0.2561	benign	-0.349	Destabilizing	0.157	N	0.527	neutral	None	None	None	None	I
P/L	0.1155	likely_benign	0.1394	benign	-0.269	Destabilizing	0.497	N	0.605	neutral	N	0.516179031	None	None	I
P/M	0.263	likely_benign	0.2976	benign	-0.264	Destabilizing	0.968	D	0.669	neutral	None	None	None	None	I
P/N	0.3178	likely_benign	0.3602	ambiguous	-0.086	Destabilizing	0.567	D	0.673	neutral	None	None	None	None	I
P/Q	0.1406	likely_benign	0.1585	benign	-0.337	Destabilizing	0.011	N	0.323	neutral	N	0.481412098	None	None	I
P/R	0.1627	likely_benign	0.1896	benign	0.153	Stabilizing	0.002	N	0.405	neutral	N	0.483324655	None	None	I
P/S	0.1411	likely_benign	0.1583	benign	-0.485	Destabilizing	0.22	N	0.535	neutral	N	0.484690554	None	None	I
P/T	0.109	likely_benign	0.1251	benign	-0.494	Destabilizing	0.497	N	0.521	neutral	N	0.490539904	None	None	I
P/V	0.166	likely_benign	0.1942	benign	-0.304	Destabilizing	0.567	D	0.598	neutral	None	None	None	None	I
P/W	0.6422	likely_pathogenic	0.7082	pathogenic	-0.783	Destabilizing	0.968	D	0.72	prob.delet.	None	None	None	None	I
P/Y	0.4363	ambiguous	0.5056	ambiguous	-0.471	Destabilizing	0.726	D	0.712	prob.delet.	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.