TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8249	24970;24971;24972	chr2:178718361;178718360;178718359	chr2:179583088;179583087;179583086
N2AB	7932	24019;24020;24021	chr2:178718361;178718360;178718359	chr2:179583088;179583087;179583086
N2A	7005	21238;21239;21240	chr2:178718361;178718360;178718359	chr2:179583088;179583087;179583086
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-67
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.5819
• 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
A/D	None	None	0.994	N	0.634	0.442	0.562990493178	gnomAD-4.0.0	1.59151E-06	None	None	None	None	I	None	0	0	None	0	2.773E-05	None	0	0	0	0	0
A/S	None	None	0.798	D	0.377	0.261	0.317667799068	gnomAD-4.0.0	6.84258E-07	None	None	None	None	I	None	0	0	None	0	0	None	1.87322E-05	0	0	0	0
A/T	None	None	0.978	D	0.534	0.434	0.408714661073	gnomAD-4.0.0	6.84258E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15958E-05	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
A/C	0.7993	likely_pathogenic	0.76	pathogenic	-0.806	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
A/D	0.7446	likely_pathogenic	0.7287	pathogenic	-0.566	Destabilizing	0.994	D	0.634	neutral	N	0.508777923	None	None	I
A/E	0.6786	likely_pathogenic	0.6457	pathogenic	-0.719	Destabilizing	0.995	D	0.532	neutral	None	None	None	None	I
A/F	0.5118	ambiguous	0.5034	ambiguous	-0.932	Destabilizing	0.99	D	0.64	neutral	None	None	None	None	I
A/G	0.3309	likely_benign	0.3228	benign	-0.191	Destabilizing	0.978	D	0.512	neutral	N	0.518270897	None	None	I
A/H	0.8322	likely_pathogenic	0.8241	pathogenic	-0.191	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
A/I	0.4757	ambiguous	0.3933	ambiguous	-0.417	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	I
A/K	0.9122	likely_pathogenic	0.8897	pathogenic	-0.467	Destabilizing	0.995	D	0.531	neutral	None	None	None	None	I
A/L	0.4795	ambiguous	0.4526	ambiguous	-0.417	Destabilizing	0.983	D	0.564	neutral	None	None	None	None	I
A/M	0.5072	ambiguous	0.4598	ambiguous	-0.526	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	I
A/N	0.6752	likely_pathogenic	0.6561	pathogenic	-0.175	Destabilizing	0.995	D	0.641	neutral	None	None	None	None	I
A/P	0.936	likely_pathogenic	0.9249	pathogenic	-0.322	Destabilizing	0.999	D	0.569	neutral	D	0.531655118	None	None	I
A/Q	0.7866	likely_pathogenic	0.7612	pathogenic	-0.451	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	I
A/R	0.8346	likely_pathogenic	0.8182	pathogenic	-0.037	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	I
A/S	0.169	likely_benign	0.1605	benign	-0.347	Destabilizing	0.798	D	0.377	neutral	D	0.536561209	None	None	I
A/T	0.2543	likely_benign	0.2156	benign	-0.432	Destabilizing	0.978	D	0.534	neutral	D	0.528359754	None	None	I
A/V	0.1983	likely_benign	0.1622	benign	-0.322	Destabilizing	0.978	D	0.531	neutral	D	0.52413063	None	None	I
A/W	0.9209	likely_pathogenic	0.9121	pathogenic	-1.019	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
A/Y	0.7287	likely_pathogenic	0.7207	pathogenic	-0.704	Destabilizing	0.643	D	0.518	neutral	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.