TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15825	47698;47699;47700	chr2:178617878;178617877;178617876	chr2:179482605;179482604;179482603
N2AB	14184	42775;42776;42777	chr2:178617878;178617877;178617876	chr2:179482605;179482604;179482603
N2A	13257	39994;39995;39996	chr2:178617878;178617877;178617876	chr2:179482605;179482604;179482603
N2B	6760	20503;20504;20505	chr2:178617878;178617877;178617876	chr2:179482605;179482604;179482603
Novex-1	6885	20878;20879;20880	chr2:178617878;178617877;178617876	chr2:179482605;179482604;179482603
Novex-2	6952	21079;21080;21081	chr2:178617878;178617877;178617876	chr2:179482605;179482604;179482603
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: Fn3-2
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.354
• 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/K	None	None	0.999	D	0.685	0.321	0.471539375507	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
E/A	0.3714	ambiguous	0.3176	benign	-0.531	Destabilizing	0.999	D	0.67	neutral	D	0.525187698	None	None	N
E/C	0.9668	likely_pathogenic	0.9599	pathogenic	-0.203	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/D	0.4847	ambiguous	0.4415	ambiguous	-0.485	Destabilizing	0.999	D	0.57	neutral	D	0.569312129	None	None	N
E/F	0.9689	likely_pathogenic	0.9639	pathogenic	-0.224	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/G	0.5904	likely_pathogenic	0.5715	pathogenic	-0.765	Destabilizing	1.0	D	0.673	neutral	D	0.573444951	None	None	N
E/H	0.9063	likely_pathogenic	0.8757	pathogenic	-0.017	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
E/I	0.7566	likely_pathogenic	0.7106	pathogenic	0.065	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/K	0.5939	likely_pathogenic	0.5242	ambiguous	0.225	Stabilizing	0.999	D	0.685	prob.neutral	D	0.529812771	None	None	N
E/L	0.8368	likely_pathogenic	0.8023	pathogenic	0.065	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/M	0.8495	likely_pathogenic	0.8328	pathogenic	0.163	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/N	0.7655	likely_pathogenic	0.7246	pathogenic	-0.263	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.6043	likely_pathogenic	0.5345	ambiguous	-0.113	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
E/Q	0.4442	ambiguous	0.3747	ambiguous	-0.208	Destabilizing	1.0	D	0.675	prob.neutral	N	0.508032616	None	None	N
E/R	0.7136	likely_pathogenic	0.6506	pathogenic	0.492	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/S	0.5849	likely_pathogenic	0.5351	ambiguous	-0.419	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
E/T	0.6659	likely_pathogenic	0.6228	pathogenic	-0.221	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/V	0.5726	likely_pathogenic	0.5186	ambiguous	-0.113	Destabilizing	1.0	D	0.681	prob.neutral	D	0.589793214	None	None	N
E/W	0.9905	likely_pathogenic	0.9883	pathogenic	0.005	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/Y	0.9445	likely_pathogenic	0.9352	pathogenic	0.038	Stabilizing	1.0	D	0.692	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.