TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20706	62341;62342;62343	chr2:178589609;178589608;178589607	chr2:179454336;179454335;179454334
N2AB	19065	57418;57419;57420	chr2:178589609;178589608;178589607	chr2:179454336;179454335;179454334
N2A	18138	54637;54638;54639	chr2:178589609;178589608;178589607	chr2:179454336;179454335;179454334
N2B	11641	35146;35147;35148	chr2:178589609;178589608;178589607	chr2:179454336;179454335;179454334
Novex-1	11766	35521;35522;35523	chr2:178589609;178589608;178589607	chr2:179454336;179454335;179454334
Novex-2	11833	35722;35723;35724	chr2:178589609;178589608;178589607	chr2:179454336;179454335;179454334
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-38
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0644
• 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	rs773156172	-2.529	0.999	N	0.685	0.363	0.402614778071	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
E/K	rs773156172	-2.529	0.999	N	0.685	0.363	0.402614778071	gnomAD-4.0.0	1.59244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8603E-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	0.9107	likely_pathogenic	0.9173	pathogenic	-1.47	Destabilizing	0.999	D	0.739	prob.delet.	D	0.523999709	None	None	N
E/C	0.9878	likely_pathogenic	0.9907	pathogenic	-0.72	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/D	0.9451	likely_pathogenic	0.9418	pathogenic	-1.916	Destabilizing	0.999	D	0.681	prob.neutral	N	0.486398848	None	None	N
E/F	0.9951	likely_pathogenic	0.9954	pathogenic	-1.272	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
E/G	0.953	likely_pathogenic	0.9511	pathogenic	-1.766	Destabilizing	1.0	D	0.777	deleterious	D	0.525774136	None	None	N
E/H	0.989	likely_pathogenic	0.9913	pathogenic	-1.075	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/I	0.9789	likely_pathogenic	0.9822	pathogenic	-0.61	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
E/K	0.9735	likely_pathogenic	0.9776	pathogenic	-1.366	Destabilizing	0.999	D	0.685	prob.neutral	N	0.504792591	None	None	N
E/L	0.9857	likely_pathogenic	0.9871	pathogenic	-0.61	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/M	0.9763	likely_pathogenic	0.981	pathogenic	-0.125	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
E/N	0.9903	likely_pathogenic	0.9911	pathogenic	-1.555	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9997	pathogenic	-0.888	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Q	0.7822	likely_pathogenic	0.7958	pathogenic	-1.289	Destabilizing	1.0	D	0.763	deleterious	N	0.473014626	None	None	N
E/R	0.9802	likely_pathogenic	0.9798	pathogenic	-1.296	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/S	0.9465	likely_pathogenic	0.9481	pathogenic	-2.023	Highly Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
E/T	0.9728	likely_pathogenic	0.9759	pathogenic	-1.725	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/V	0.9414	likely_pathogenic	0.9539	pathogenic	-0.888	Destabilizing	1.0	D	0.779	deleterious	N	0.513403873	None	None	N
E/W	0.9982	likely_pathogenic	0.998	pathogenic	-1.456	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/Y	0.9934	likely_pathogenic	0.9944	pathogenic	-1.162	Destabilizing	1.0	D	0.841	deleterious	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.