TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26899	80920;80921;80922	chr2:178565437;178565436;178565435	chr2:179430164;179430163;179430162
N2AB	25258	75997;75998;75999	chr2:178565437;178565436;178565435	chr2:179430164;179430163;179430162
N2A	24331	73216;73217;73218	chr2:178565437;178565436;178565435	chr2:179430164;179430163;179430162
N2B	17834	53725;53726;53727	chr2:178565437;178565436;178565435	chr2:179430164;179430163;179430162
Novex-1	17959	54100;54101;54102	chr2:178565437;178565436;178565435	chr2:179430164;179430163;179430162
Novex-2	18026	54301;54302;54303	chr2:178565437;178565436;178565435	chr2:179430164;179430163;179430162
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-139
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.169
• 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
I/R	None	None	0.971	D	0.832	0.717	0.831722884016	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.6217	likely_pathogenic	0.569	pathogenic	-2.279	Highly Destabilizing	0.754	D	0.682	prob.neutral	None	None	None	None	N
I/C	0.8718	likely_pathogenic	0.8789	pathogenic	-1.592	Destabilizing	0.994	D	0.711	prob.delet.	None	None	None	None	N
I/D	0.9947	likely_pathogenic	0.9942	pathogenic	-2.711	Highly Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
I/E	0.9832	likely_pathogenic	0.9822	pathogenic	-2.47	Highly Destabilizing	0.978	D	0.831	deleterious	None	None	None	None	N
I/F	0.3569	ambiguous	0.3533	ambiguous	-1.525	Destabilizing	0.956	D	0.691	prob.neutral	None	None	None	None	N
I/G	0.9507	likely_pathogenic	0.9436	pathogenic	-2.742	Highly Destabilizing	0.978	D	0.821	deleterious	None	None	None	None	N
I/H	0.9809	likely_pathogenic	0.9824	pathogenic	-2.086	Highly Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
I/K	0.9653	likely_pathogenic	0.9686	pathogenic	-1.836	Destabilizing	0.971	D	0.829	deleterious	D	0.522043105	None	None	N
I/L	0.1445	likely_benign	0.1534	benign	-0.918	Destabilizing	0.294	N	0.421	neutral	N	0.408255103	None	None	N
I/M	0.148	likely_benign	0.1364	benign	-0.915	Destabilizing	0.942	D	0.661	neutral	D	0.531480676	None	None	N
I/N	0.9536	likely_pathogenic	0.9539	pathogenic	-2.349	Highly Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
I/P	0.9844	likely_pathogenic	0.9804	pathogenic	-1.359	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
I/Q	0.9691	likely_pathogenic	0.971	pathogenic	-2.144	Highly Destabilizing	0.993	D	0.831	deleterious	None	None	None	None	N
I/R	0.9453	likely_pathogenic	0.95	pathogenic	-1.739	Destabilizing	0.971	D	0.832	deleterious	D	0.54014736	None	None	N
I/S	0.9022	likely_pathogenic	0.8831	pathogenic	-2.907	Highly Destabilizing	0.956	D	0.796	deleterious	None	None	None	None	N
I/T	0.6772	likely_pathogenic	0.6128	pathogenic	-2.519	Highly Destabilizing	0.822	D	0.724	prob.delet.	D	0.539893871	None	None	N
I/V	0.0883	likely_benign	0.085	benign	-1.359	Destabilizing	0.006	N	0.22	neutral	N	0.498349538	None	None	N
I/W	0.9449	likely_pathogenic	0.9422	pathogenic	-1.758	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
I/Y	0.8615	likely_pathogenic	0.8784	pathogenic	-1.498	Destabilizing	0.978	D	0.714	prob.delet.	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.