TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1473	4642;4643;4644	chr2:178777767;178777766;178777765	chr2:179642494;179642493;179642492
N2AB	1473	4642;4643;4644	chr2:178777767;178777766;178777765	chr2:179642494;179642493;179642492
N2A	1473	4642;4643;4644	chr2:178777767;178777766;178777765	chr2:179642494;179642493;179642492
N2B	1427	4504;4505;4506	chr2:178777767;178777766;178777765	chr2:179642494;179642493;179642492
Novex-1	1427	4504;4505;4506	chr2:178777767;178777766;178777765	chr2:179642494;179642493;179642492
Novex-2	1427	4504;4505;4506	chr2:178777767;178777766;178777765	chr2:179642494;179642493;179642492
Novex-3	1473	4642;4643;4644	chr2:178777767;178777766;178777765	chr2:179642494;179642493;179642492

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-6
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4425
• 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
T/S	None	None	0.999	N	0.534	0.211	0.180583059064	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
T/A	0.3622	ambiguous	0.3637	ambiguous	-0.65	Destabilizing	0.999	D	0.533	neutral	N	0.508308856	None	None	I
T/C	0.9334	likely_pathogenic	0.9306	pathogenic	-0.45	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
T/D	0.9577	likely_pathogenic	0.9603	pathogenic	0.131	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
T/E	0.9145	likely_pathogenic	0.9196	pathogenic	0.122	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
T/F	0.8955	likely_pathogenic	0.9047	pathogenic	-0.757	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
T/G	0.8539	likely_pathogenic	0.8581	pathogenic	-0.89	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
T/H	0.8996	likely_pathogenic	0.9045	pathogenic	-1.104	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
T/I	0.6976	likely_pathogenic	0.7157	pathogenic	-0.111	Destabilizing	1.0	D	0.776	deleterious	D	0.597108609	None	None	I
T/K	0.8661	likely_pathogenic	0.8798	pathogenic	-0.589	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
T/L	0.4931	ambiguous	0.5046	ambiguous	-0.111	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
T/M	0.2917	likely_benign	0.3068	benign	0.011	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
T/N	0.6503	likely_pathogenic	0.6605	pathogenic	-0.491	Destabilizing	1.0	D	0.764	deleterious	N	0.509703734	None	None	I
T/P	0.4258	ambiguous	0.4203	ambiguous	-0.258	Destabilizing	1.0	D	0.769	deleterious	N	0.502329142	None	None	I
T/Q	0.8448	likely_pathogenic	0.8523	pathogenic	-0.63	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
T/R	0.8556	likely_pathogenic	0.8717	pathogenic	-0.361	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
T/S	0.5463	ambiguous	0.5449	ambiguous	-0.79	Destabilizing	0.999	D	0.534	neutral	N	0.503658847	None	None	I
T/V	0.5135	ambiguous	0.5184	ambiguous	-0.258	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
T/W	0.9737	likely_pathogenic	0.9756	pathogenic	-0.706	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
T/Y	0.9035	likely_pathogenic	0.9134	pathogenic	-0.464	Destabilizing	1.0	D	0.789	deleterious	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.