TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28686	86281;86282;86283	chr2:178560076;178560075;178560074	chr2:179424803;179424802;179424801
N2AB	27045	81358;81359;81360	chr2:178560076;178560075;178560074	chr2:179424803;179424802;179424801
N2A	26118	78577;78578;78579	chr2:178560076;178560075;178560074	chr2:179424803;179424802;179424801
N2B	19621	59086;59087;59088	chr2:178560076;178560075;178560074	chr2:179424803;179424802;179424801
Novex-1	19746	59461;59462;59463	chr2:178560076;178560075;178560074	chr2:179424803;179424802;179424801
Novex-2	19813	59662;59663;59664	chr2:178560076;178560075;178560074	chr2:179424803;179424802;179424801
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-97
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1208
• 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	rs868813015	-1.776	1.0	D	0.851	0.858	0.861789863285	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
Y/C	rs868813015	-1.776	1.0	D	0.851	0.858	0.861789863285	gnomAD-4.0.0	6.15817E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19564E-06	0	1.65656E-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
Y/A	0.9961	likely_pathogenic	0.9957	pathogenic	-3.175	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
Y/C	0.8836	likely_pathogenic	0.8508	pathogenic	-1.754	Destabilizing	1.0	D	0.851	deleterious	D	0.652119694	None	None	N
Y/D	0.9938	likely_pathogenic	0.994	pathogenic	-3.378	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.652321498	None	None	N
Y/E	0.9985	likely_pathogenic	0.9984	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/F	0.2854	likely_benign	0.2445	benign	-1.109	Destabilizing	0.999	D	0.641	neutral	D	0.556055326	None	None	N
Y/G	0.991	likely_pathogenic	0.9899	pathogenic	-3.601	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/H	0.9618	likely_pathogenic	0.9483	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.783	deleterious	D	0.635696725	None	None	N
Y/I	0.9696	likely_pathogenic	0.9672	pathogenic	-1.747	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/K	0.9979	likely_pathogenic	0.9979	pathogenic	-2.051	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
Y/L	0.9477	likely_pathogenic	0.9498	pathogenic	-1.747	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
Y/M	0.9779	likely_pathogenic	0.9764	pathogenic	-1.589	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
Y/N	0.9561	likely_pathogenic	0.9534	pathogenic	-2.821	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.652119694	None	None	N
Y/P	0.9993	likely_pathogenic	0.9993	pathogenic	-2.24	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/Q	0.9967	likely_pathogenic	0.9958	pathogenic	-2.551	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/R	0.9934	likely_pathogenic	0.9928	pathogenic	-1.907	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
Y/S	0.9813	likely_pathogenic	0.979	pathogenic	-3.197	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.652119694	None	None	N
Y/T	0.9934	likely_pathogenic	0.9925	pathogenic	-2.845	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/V	0.9524	likely_pathogenic	0.95	pathogenic	-2.24	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
Y/W	0.8665	likely_pathogenic	0.8374	pathogenic	-0.292	Destabilizing	1.0	D	0.775	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.