TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27075	81448;81449;81450	chr2:178564909;178564908;178564907	chr2:179429636;179429635;179429634
N2AB	25434	76525;76526;76527	chr2:178564909;178564908;178564907	chr2:179429636;179429635;179429634
N2A	24507	73744;73745;73746	chr2:178564909;178564908;178564907	chr2:179429636;179429635;179429634
N2B	18010	54253;54254;54255	chr2:178564909;178564908;178564907	chr2:179429636;179429635;179429634
Novex-1	18135	54628;54629;54630	chr2:178564909;178564908;178564907	chr2:179429636;179429635;179429634
Novex-2	18202	54829;54830;54831	chr2:178564909;178564908;178564907	chr2:179429636;179429635;179429634
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-85
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3768
• 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
P/S	None	None	0.956	N	0.656	0.305	0.321108458156	gnomAD-4.0.0	1.36959E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.70963E-05	0	1.65859E-05
P/T	None	None	0.978	N	0.697	0.323	0.377097596864	gnomAD-4.0.0	6.84796E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16393E-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
P/A	0.0948	likely_benign	0.0934	benign	-1.293	Destabilizing	0.198	N	0.375	neutral	N	0.448077354	None	None	I
P/C	0.5463	ambiguous	0.5499	ambiguous	-0.996	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
P/D	0.9157	likely_pathogenic	0.9254	pathogenic	-1.135	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
P/E	0.6315	likely_pathogenic	0.6414	pathogenic	-1.192	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	I
P/F	0.6886	likely_pathogenic	0.6711	pathogenic	-1.264	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	I
P/G	0.6257	likely_pathogenic	0.641	pathogenic	-1.534	Destabilizing	0.967	D	0.723	prob.delet.	None	None	None	None	I
P/H	0.4876	ambiguous	0.493	ambiguous	-1.034	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
P/I	0.4424	ambiguous	0.4095	ambiguous	-0.756	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	I
P/K	0.6725	likely_pathogenic	0.6622	pathogenic	-0.917	Destabilizing	0.995	D	0.701	prob.neutral	None	None	None	None	I
P/L	0.2475	likely_benign	0.234	benign	-0.756	Destabilizing	0.978	D	0.789	deleterious	N	0.507683108	None	None	I
P/M	0.421	ambiguous	0.3966	ambiguous	-0.561	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/N	0.7009	likely_pathogenic	0.7153	pathogenic	-0.667	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
P/Q	0.3179	likely_benign	0.3113	benign	-0.951	Destabilizing	0.999	D	0.688	prob.neutral	N	0.480727308	None	None	I
P/R	0.5249	ambiguous	0.5179	ambiguous	-0.368	Destabilizing	0.997	D	0.767	deleterious	N	0.495059355	None	None	I
P/S	0.2259	likely_benign	0.2364	benign	-1.159	Destabilizing	0.956	D	0.656	neutral	N	0.472244612	None	None	I
P/T	0.2495	likely_benign	0.2487	benign	-1.115	Destabilizing	0.978	D	0.697	prob.neutral	N	0.485780191	None	None	I
P/V	0.32	likely_benign	0.2989	benign	-0.9	Destabilizing	0.983	D	0.747	deleterious	None	None	None	None	I
P/W	0.8891	likely_pathogenic	0.8942	pathogenic	-1.338	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
P/Y	0.7242	likely_pathogenic	0.7266	pathogenic	-1.044	Destabilizing	0.999	D	0.815	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.