TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20098	60517;60518;60519	chr2:178591433;178591432;178591431	chr2:179456160;179456159;179456158
N2AB	18457	55594;55595;55596	chr2:178591433;178591432;178591431	chr2:179456160;179456159;179456158
N2A	17530	52813;52814;52815	chr2:178591433;178591432;178591431	chr2:179456160;179456159;179456158
N2B	11033	33322;33323;33324	chr2:178591433;178591432;178591431	chr2:179456160;179456159;179456158
Novex-1	11158	33697;33698;33699	chr2:178591433;178591432;178591431	chr2:179456160;179456159;179456158
Novex-2	11225	33898;33899;33900	chr2:178591433;178591432;178591431	chr2:179456160;179456159;179456158
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-120
• Domain position: 19
• Structural Position: 30
• Q(SASA): 0.1111
• 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
F/S	None	None	0.784	D	0.716	0.679	0.727926503626	gnomAD-4.0.0	2.75181E-06	None	None	None	None	N	None	0	0	None	0	2.52398E-05	None	0	0	2.7068E-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
F/A	0.987	likely_pathogenic	0.9864	pathogenic	-1.798	Destabilizing	0.495	N	0.671	neutral	None	None	None	None	N
F/C	0.8424	likely_pathogenic	0.8334	pathogenic	-1.49	Destabilizing	0.975	D	0.814	deleterious	D	0.559016335	None	None	N
F/D	0.999	likely_pathogenic	0.9988	pathogenic	-3.032	Highly Destabilizing	0.981	D	0.793	deleterious	None	None	None	None	N
F/E	0.9982	likely_pathogenic	0.9979	pathogenic	-2.819	Highly Destabilizing	0.936	D	0.763	deleterious	None	None	None	None	N
F/G	0.9965	likely_pathogenic	0.9961	pathogenic	-2.185	Highly Destabilizing	0.936	D	0.727	prob.delet.	None	None	None	None	N
F/H	0.9876	likely_pathogenic	0.985	pathogenic	-1.91	Destabilizing	0.981	D	0.735	prob.delet.	None	None	None	None	N
F/I	0.2688	likely_benign	0.2696	benign	-0.532	Destabilizing	0.139	N	0.457	neutral	N	0.441640611	None	None	N
F/K	0.9974	likely_pathogenic	0.9968	pathogenic	-2.222	Highly Destabilizing	0.828	D	0.741	deleterious	None	None	None	None	N
F/L	0.7264	likely_pathogenic	0.7418	pathogenic	-0.532	Destabilizing	0.001	N	0.246	neutral	N	0.363013964	None	None	N
F/M	0.64	likely_pathogenic	0.65	pathogenic	-0.545	Destabilizing	0.893	D	0.655	neutral	None	None	None	None	N
F/N	0.9952	likely_pathogenic	0.9944	pathogenic	-2.945	Highly Destabilizing	0.981	D	0.803	deleterious	None	None	None	None	N
F/P	0.9994	likely_pathogenic	0.9993	pathogenic	-0.965	Destabilizing	0.981	D	0.802	deleterious	None	None	None	None	N
F/Q	0.9955	likely_pathogenic	0.9947	pathogenic	-2.595	Highly Destabilizing	0.981	D	0.815	deleterious	None	None	None	None	N
F/R	0.9949	likely_pathogenic	0.9941	pathogenic	-2.402	Highly Destabilizing	0.944	D	0.793	deleterious	None	None	None	None	N
F/S	0.9929	likely_pathogenic	0.9921	pathogenic	-3.18	Highly Destabilizing	0.784	D	0.716	prob.delet.	D	0.559016335	None	None	N
F/T	0.9909	likely_pathogenic	0.9898	pathogenic	-2.848	Highly Destabilizing	0.495	N	0.697	prob.neutral	None	None	None	None	N
F/V	0.5152	ambiguous	0.5088	ambiguous	-0.965	Destabilizing	0.01	N	0.483	neutral	N	0.47842813	None	None	N
F/W	0.8962	likely_pathogenic	0.8893	pathogenic	-0.447	Destabilizing	0.995	D	0.609	neutral	None	None	None	None	N
F/Y	0.6075	likely_pathogenic	0.5801	pathogenic	-0.728	Destabilizing	0.784	D	0.531	neutral	D	0.546775789	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.