TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23262	70009;70010;70011	chr2:178576348;178576347;178576346	chr2:179441075;179441074;179441073
N2AB	21621	65086;65087;65088	chr2:178576348;178576347;178576346	chr2:179441075;179441074;179441073
N2A	20694	62305;62306;62307	chr2:178576348;178576347;178576346	chr2:179441075;179441074;179441073
N2B	14197	42814;42815;42816	chr2:178576348;178576347;178576346	chr2:179441075;179441074;179441073
Novex-1	14322	43189;43190;43191	chr2:178576348;178576347;178576346	chr2:179441075;179441074;179441073
Novex-2	14389	43390;43391;43392	chr2:178576348;178576347;178576346	chr2:179441075;179441074;179441073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-57
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.2124
• 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
G/C	None	None	0.997	N	0.853	0.362	0.354610295913	gnomAD-4.0.0	2.84202E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.74815E-06	0	1.72366E-05
G/S	None	None	0.085	N	0.365	0.079	0.107399877778	gnomAD-4.0.0	7.10502E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.72366E-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	0.1992	likely_benign	0.2095	benign	-0.666	Destabilizing	0.865	D	0.515	neutral	N	0.439730017	None	None	I
G/C	0.2953	likely_benign	0.2913	benign	-0.851	Destabilizing	0.997	D	0.853	deleterious	N	0.4752481	None	None	I
G/D	0.5413	ambiguous	0.5016	ambiguous	-1.532	Destabilizing	0.978	D	0.725	prob.delet.	N	0.437612431	None	None	I
G/E	0.4427	ambiguous	0.4212	ambiguous	-1.496	Destabilizing	0.968	D	0.708	prob.delet.	None	None	None	None	I
G/F	0.7754	likely_pathogenic	0.7603	pathogenic	-0.897	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	I
G/H	0.6327	likely_pathogenic	0.602	pathogenic	-1.681	Destabilizing	0.998	D	0.842	deleterious	None	None	None	None	I
G/I	0.4536	ambiguous	0.4492	ambiguous	0.026	Stabilizing	0.983	D	0.859	deleterious	None	None	None	None	I
G/K	0.6571	likely_pathogenic	0.6122	pathogenic	-1.311	Destabilizing	0.968	D	0.739	prob.delet.	None	None	None	None	I
G/L	0.5567	ambiguous	0.5534	ambiguous	0.026	Stabilizing	0.983	D	0.803	deleterious	None	None	None	None	I
G/M	0.5715	likely_pathogenic	0.5762	pathogenic	-0.008	Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	I
G/N	0.387	ambiguous	0.3549	ambiguous	-1.126	Destabilizing	0.968	D	0.717	prob.delet.	None	None	None	None	I
G/P	0.9796	likely_pathogenic	0.976	pathogenic	-0.16	Destabilizing	0.992	D	0.817	deleterious	None	None	None	None	I
G/Q	0.4954	ambiguous	0.4782	ambiguous	-1.149	Destabilizing	0.547	D	0.476	neutral	None	None	None	None	I
G/R	0.5318	ambiguous	0.4989	ambiguous	-1.193	Destabilizing	0.957	D	0.795	deleterious	N	0.430667816	None	None	I
G/S	0.1198	likely_benign	0.1218	benign	-1.385	Destabilizing	0.085	N	0.365	neutral	N	0.376254541	None	None	I
G/T	0.2099	likely_benign	0.2152	benign	-1.248	Destabilizing	0.968	D	0.751	deleterious	None	None	None	None	I
G/V	0.3211	likely_benign	0.3261	benign	-0.16	Destabilizing	0.978	D	0.817	deleterious	N	0.474728025	None	None	I
G/W	0.694	likely_pathogenic	0.6572	pathogenic	-1.494	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	I
G/Y	0.6635	likely_pathogenic	0.6363	pathogenic	-0.957	Destabilizing	0.999	D	0.857	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.