TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18098	54517;54518;54519	chr2:178604797;178604796;178604795	chr2:179469524;179469523;179469522
N2AB	16457	49594;49595;49596	chr2:178604797;178604796;178604795	chr2:179469524;179469523;179469522
N2A	15530	46813;46814;46815	chr2:178604797;178604796;178604795	chr2:179469524;179469523;179469522
N2B	9033	27322;27323;27324	chr2:178604797;178604796;178604795	chr2:179469524;179469523;179469522
Novex-1	9158	27697;27698;27699	chr2:178604797;178604796;178604795	chr2:179469524;179469523;179469522
Novex-2	9225	27898;27899;27900	chr2:178604797;178604796;178604795	chr2:179469524;179469523;179469522
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-19
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.2176
• Predicted PPI site: I

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
T/A	None	None	0.999	N	0.523	0.564	0.383256108077	gnomAD-4.0.0	1.36946E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.8E-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
T/A	0.2322	likely_benign	0.2372	benign	-0.691	Destabilizing	0.999	D	0.523	neutral	N	0.498693432	None	None	I
T/C	0.7155	likely_pathogenic	0.7037	pathogenic	-0.414	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
T/D	0.7268	likely_pathogenic	0.6964	pathogenic	-0.284	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
T/E	0.6569	likely_pathogenic	0.6399	pathogenic	-0.279	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
T/F	0.543	ambiguous	0.533	ambiguous	-0.649	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
T/G	0.5002	ambiguous	0.4886	ambiguous	-0.963	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
T/H	0.5927	likely_pathogenic	0.5566	ambiguous	-1.224	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
T/I	0.3846	ambiguous	0.3971	ambiguous	-0.057	Destabilizing	1.0	D	0.777	deleterious	D	0.523447478	None	None	I
T/K	0.6086	likely_pathogenic	0.572	pathogenic	-0.839	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
T/L	0.1782	likely_benign	0.1877	benign	-0.057	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	I
T/M	0.1573	likely_benign	0.1665	benign	0.14	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
T/N	0.2864	likely_benign	0.2788	benign	-0.75	Destabilizing	1.0	D	0.775	deleterious	N	0.487679522	None	None	I
T/P	0.7496	likely_pathogenic	0.7494	pathogenic	-0.235	Destabilizing	1.0	D	0.764	deleterious	D	0.526965905	None	None	I
T/Q	0.519	ambiguous	0.4977	ambiguous	-0.87	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
T/R	0.5919	likely_pathogenic	0.5476	ambiguous	-0.606	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
T/S	0.1657	likely_benign	0.1537	benign	-0.985	Destabilizing	0.999	D	0.515	neutral	N	0.51028618	None	None	I
T/V	0.3245	likely_benign	0.3319	benign	-0.235	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	I
T/W	0.8766	likely_pathogenic	0.8639	pathogenic	-0.631	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
T/Y	0.6322	likely_pathogenic	0.6274	pathogenic	-0.413	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I

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.