TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2777	8554;8555;8556	chr2:178770463;178770462;178770461	chr2:179635190;179635189;179635188
N2AB	2777	8554;8555;8556	chr2:178770463;178770462;178770461	chr2:179635190;179635189;179635188
N2A	2777	8554;8555;8556	chr2:178770463;178770462;178770461	chr2:179635190;179635189;179635188
N2B	2731	8416;8417;8418	chr2:178770463;178770462;178770461	chr2:179635190;179635189;179635188
Novex-1	2731	8416;8417;8418	chr2:178770463;178770462;178770461	chr2:179635190;179635189;179635188
Novex-2	2731	8416;8417;8418	chr2:178770463;178770462;178770461	chr2:179635190;179635189;179635188
Novex-3	2777	8554;8555;8556	chr2:178770463;178770462;178770461	chr2:179635190;179635189;179635188

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-17
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1235
• 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	None	None	1.0	D	0.838	0.959	0.93031496195	gnomAD-4.0.0	1.36815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79859E-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	0.9661	likely_pathogenic	0.979	pathogenic	-1.803	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/C	0.6303	likely_pathogenic	0.7325	pathogenic	-1.675	Destabilizing	1.0	D	0.838	deleterious	D	0.675034475	None	None	N
Y/D	0.9939	likely_pathogenic	0.9961	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.675034475	None	None	N
Y/E	0.9957	likely_pathogenic	0.9971	pathogenic	-1.902	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/F	0.1673	likely_benign	0.1743	benign	-0.653	Destabilizing	0.999	D	0.711	prob.delet.	D	0.625895629	None	None	N
Y/G	0.9703	likely_pathogenic	0.9822	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/H	0.9243	likely_pathogenic	0.9482	pathogenic	-1.411	Destabilizing	1.0	D	0.798	deleterious	D	0.675340558	None	None	N
Y/I	0.6711	likely_pathogenic	0.7238	pathogenic	-0.556	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/K	0.9964	likely_pathogenic	0.9975	pathogenic	-1.813	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/L	0.64	likely_pathogenic	0.7063	pathogenic	-0.556	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
Y/M	0.9236	likely_pathogenic	0.9394	pathogenic	-0.742	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/N	0.9621	likely_pathogenic	0.9763	pathogenic	-2.628	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.675034475	None	None	N
Y/P	0.9899	likely_pathogenic	0.9938	pathogenic	-0.98	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/Q	0.9941	likely_pathogenic	0.9962	pathogenic	-2.187	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/R	0.9821	likely_pathogenic	0.9878	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/S	0.9482	likely_pathogenic	0.9688	pathogenic	-2.991	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.675034475	None	None	N
Y/T	0.9592	likely_pathogenic	0.9749	pathogenic	-2.647	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/V	0.5706	likely_pathogenic	0.6355	pathogenic	-0.98	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
Y/W	0.7708	likely_pathogenic	0.7855	pathogenic	-0.179	Destabilizing	1.0	D	0.785	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.