TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21997	66214;66215;66216	chr2:178582467;178582466;178582465	chr2:179447194;179447193;179447192
N2AB	20356	61291;61292;61293	chr2:178582467;178582466;178582465	chr2:179447194;179447193;179447192
N2A	19429	58510;58511;58512	chr2:178582467;178582466;178582465	chr2:179447194;179447193;179447192
N2B	12932	39019;39020;39021	chr2:178582467;178582466;178582465	chr2:179447194;179447193;179447192
Novex-1	13057	39394;39395;39396	chr2:178582467;178582466;178582465	chr2:179447194;179447193;179447192
Novex-2	13124	39595;39596;39597	chr2:178582467;178582466;178582465	chr2:179447194;179447193;179447192
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-47
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2099
• 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
E/G	None	None	0.999	N	0.674	0.576	0.491729458163	gnomAD-4.0.0	2.40067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62503E-06	0	0
E/K	rs1228774408	-1.287	0.998	N	0.503	0.333	0.37097340754	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
E/K	rs1228774408	-1.287	0.998	N	0.503	0.333	0.37097340754	gnomAD-4.0.0	3.18629E-06	None	None	None	None	N	None	0	4.57687E-05	None	0	0	None	0	0	0	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
E/A	0.9784	likely_pathogenic	0.9754	pathogenic	-0.875	Destabilizing	0.998	D	0.578	neutral	N	0.494792638	None	None	N
E/C	0.9976	likely_pathogenic	0.9979	pathogenic	-0.579	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/D	0.9462	likely_pathogenic	0.9216	pathogenic	-1.48	Destabilizing	0.434	N	0.194	neutral	N	0.464417817	None	None	N
E/F	0.9994	likely_pathogenic	0.9994	pathogenic	-0.195	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/G	0.9828	likely_pathogenic	0.9812	pathogenic	-1.31	Destabilizing	0.999	D	0.674	neutral	N	0.504200388	None	None	N
E/H	0.9973	likely_pathogenic	0.9973	pathogenic	-0.603	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/I	0.9954	likely_pathogenic	0.9952	pathogenic	0.335	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/K	0.9864	likely_pathogenic	0.9862	pathogenic	-1.02	Destabilizing	0.998	D	0.503	neutral	N	0.467178502	None	None	N
E/L	0.9966	likely_pathogenic	0.9958	pathogenic	0.335	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/M	0.9953	likely_pathogenic	0.9949	pathogenic	0.921	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/N	0.9938	likely_pathogenic	0.9924	pathogenic	-1.544	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/P	0.9967	likely_pathogenic	0.9957	pathogenic	-0.047	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/Q	0.9564	likely_pathogenic	0.9561	pathogenic	-1.318	Destabilizing	0.999	D	0.637	neutral	N	0.484295253	None	None	N
E/R	0.9889	likely_pathogenic	0.9887	pathogenic	-0.758	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/S	0.9899	likely_pathogenic	0.9873	pathogenic	-1.947	Destabilizing	0.997	D	0.536	neutral	None	None	None	None	N
E/T	0.9959	likely_pathogenic	0.9958	pathogenic	-1.575	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/V	0.9887	likely_pathogenic	0.9873	pathogenic	-0.047	Destabilizing	1.0	D	0.787	deleterious	N	0.507162902	None	None	N
E/W	0.9997	likely_pathogenic	0.9997	pathogenic	-0.008	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9988	likely_pathogenic	0.9987	pathogenic	0.035	Stabilizing	1.0	D	0.793	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.