TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6422	19489;19490;19491	chr2:178728662;178728661;178728660	chr2:179593389;179593388;179593387
N2AB	6105	18538;18539;18540	chr2:178728662;178728661;178728660	chr2:179593389;179593388;179593387
N2A	5178	15757;15758;15759	chr2:178728662;178728661;178728660	chr2:179593389;179593388;179593387
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: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-48
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.393
• 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
G/R	rs774524508	-0.39	1.0	D	0.665	0.599	0.763780976484	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	1.20212E-04	1.57E-05	1.41243E-04
G/R	rs774524508	-0.39	1.0	D	0.665	0.599	0.763780976484	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
G/R	rs774524508	-0.39	1.0	D	0.665	0.599	0.763780976484	gnomAD-4.0.0	2.35562E-05	None	None	None	None	N	None	2.67115E-05	0	None	0	0	None	6.25547E-05	0	2.54332E-05	0	3.2039E-05

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
G/A	0.42	ambiguous	0.4314	ambiguous	-0.299	Destabilizing	0.996	D	0.509	neutral	N	0.507600067	None	None	N
G/C	0.5679	likely_pathogenic	0.5614	ambiguous	-0.927	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
G/D	0.2281	likely_benign	0.2069	benign	-0.717	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
G/E	0.3052	likely_benign	0.2561	benign	-0.886	Destabilizing	0.884	D	0.387	neutral	N	0.485822054	None	None	N
G/F	0.898	likely_pathogenic	0.8974	pathogenic	-1.055	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
G/H	0.5566	ambiguous	0.5385	ambiguous	-0.461	Destabilizing	0.844	D	0.429	neutral	None	None	None	None	N
G/I	0.8271	likely_pathogenic	0.8227	pathogenic	-0.508	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
G/K	0.52	ambiguous	0.4366	ambiguous	-0.856	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
G/L	0.8512	likely_pathogenic	0.8527	pathogenic	-0.508	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
G/M	0.824	likely_pathogenic	0.8253	pathogenic	-0.573	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
G/N	0.2786	likely_benign	0.2824	benign	-0.509	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
G/P	0.9896	likely_pathogenic	0.9919	pathogenic	-0.408	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
G/Q	0.3722	ambiguous	0.3446	ambiguous	-0.81	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
G/R	0.3704	ambiguous	0.3213	benign	-0.367	Destabilizing	1.0	D	0.665	neutral	D	0.543555087	None	None	N
G/S	0.1449	likely_benign	0.1528	benign	-0.623	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
G/T	0.4988	ambiguous	0.5028	ambiguous	-0.729	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
G/V	0.7431	likely_pathogenic	0.7371	pathogenic	-0.408	Destabilizing	0.999	D	0.695	prob.neutral	D	0.533466229	None	None	N
G/W	0.7207	likely_pathogenic	0.7216	pathogenic	-1.181	Destabilizing	1.0	D	0.683	prob.neutral	D	0.544822535	None	None	N
G/Y	0.7766	likely_pathogenic	0.761	pathogenic	-0.858	Destabilizing	0.999	D	0.722	prob.delet.	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.