TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33552	100879;100880;100881	chr2:178536093;178536092;178536091	chr2:179400820;179400819;179400818
N2AB	31911	95956;95957;95958	chr2:178536093;178536092;178536091	chr2:179400820;179400819;179400818
N2A	30984	93175;93176;93177	chr2:178536093;178536092;178536091	chr2:179400820;179400819;179400818
N2B	24487	73684;73685;73686	chr2:178536093;178536092;178536091	chr2:179400820;179400819;179400818
Novex-1	24612	74059;74060;74061	chr2:178536093;178536092;178536091	chr2:179400820;179400819;179400818
Novex-2	24679	74260;74261;74262	chr2:178536093;178536092;178536091	chr2:179400820;179400819;179400818
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-158
• Domain position: 57
• Structural Position: 135
• Q(SASA): 0.2771
• 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
Y/C	rs768683486	-0.731	1.0	D	0.735	0.517	0.682531388322	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Y/C	rs768683486	-0.731	1.0	D	0.735	0.517	0.682531388322	gnomAD-4.0.0	2.05619E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70299E-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
Y/A	0.9879	likely_pathogenic	0.9567	pathogenic	-2.395	Highly Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
Y/C	0.884	likely_pathogenic	0.6883	pathogenic	-0.799	Destabilizing	1.0	D	0.735	prob.delet.	D	0.526458859	None	None	N
Y/D	0.9888	likely_pathogenic	0.9485	pathogenic	-1.102	Destabilizing	1.0	D	0.784	deleterious	N	0.4813585	None	None	N
Y/E	0.9968	likely_pathogenic	0.9822	pathogenic	-1.024	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
Y/F	0.3212	likely_benign	0.2123	benign	-1.112	Destabilizing	0.996	D	0.503	neutral	N	0.486689749	None	None	N
Y/G	0.977	likely_pathogenic	0.9398	pathogenic	-2.715	Highly Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
Y/H	0.949	likely_pathogenic	0.8018	pathogenic	-1.15	Destabilizing	1.0	D	0.707	prob.neutral	N	0.507006306	None	None	N
Y/I	0.9544	likely_pathogenic	0.8796	pathogenic	-1.42	Destabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
Y/K	0.9936	likely_pathogenic	0.9742	pathogenic	-1.095	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
Y/L	0.924	likely_pathogenic	0.8447	pathogenic	-1.42	Destabilizing	0.991	D	0.672	neutral	None	None	None	None	N
Y/M	0.9745	likely_pathogenic	0.9251	pathogenic	-0.93	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
Y/N	0.9295	likely_pathogenic	0.7736	pathogenic	-1.345	Destabilizing	1.0	D	0.772	deleterious	N	0.472200299	None	None	N
Y/P	0.9974	likely_pathogenic	0.9928	pathogenic	-1.741	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
Y/Q	0.9934	likely_pathogenic	0.9634	pathogenic	-1.324	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
Y/R	0.9837	likely_pathogenic	0.9391	pathogenic	-0.597	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
Y/S	0.945	likely_pathogenic	0.8245	pathogenic	-1.868	Destabilizing	1.0	D	0.753	deleterious	N	0.451921028	None	None	N
Y/T	0.9798	likely_pathogenic	0.9245	pathogenic	-1.696	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
Y/V	0.9371	likely_pathogenic	0.8471	pathogenic	-1.741	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
Y/W	0.8743	likely_pathogenic	0.7409	pathogenic	-0.713	Destabilizing	1.0	D	0.683	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.