TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16980	51163;51164;51165	chr2:178611191;178611190;178611189	chr2:179475918;179475917;179475916
N2AB	15339	46240;46241;46242	chr2:178611191;178611190;178611189	chr2:179475918;179475917;179475916
N2A	14412	43459;43460;43461	chr2:178611191;178611190;178611189	chr2:179475918;179475917;179475916
N2B	7915	23968;23969;23970	chr2:178611191;178611190;178611189	chr2:179475918;179475917;179475916
Novex-1	8040	24343;24344;24345	chr2:178611191;178611190;178611189	chr2:179475918;179475917;179475916
Novex-2	8107	24544;24545;24546	chr2:178611191;178611190;178611189	chr2:179475918;179475917;179475916
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-111
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.1335
• 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
A/T	None	None	0.955	D	0.692	0.458	0.493156425868	gnomAD-4.0.0	3.1869E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72357E-06	0	0
A/V	None	None	0.977	D	0.73	0.542	0.583551733957	gnomAD-4.0.0	1.59345E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8618E-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
A/C	0.8534	likely_pathogenic	0.8267	pathogenic	-0.654	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
A/D	0.9903	likely_pathogenic	0.9836	pathogenic	-1.476	Destabilizing	0.993	D	0.761	deleterious	D	0.657983381	None	None	I
A/E	0.9934	likely_pathogenic	0.9891	pathogenic	-1.407	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	I
A/F	0.9824	likely_pathogenic	0.9734	pathogenic	-0.702	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
A/G	0.1808	likely_benign	0.1536	benign	-1.158	Destabilizing	0.955	D	0.543	neutral	N	0.433438928	None	None	I
A/H	0.9931	likely_pathogenic	0.9887	pathogenic	-1.604	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
A/I	0.9844	likely_pathogenic	0.9763	pathogenic	0.067	Stabilizing	0.998	D	0.797	deleterious	None	None	None	None	I
A/K	0.9986	likely_pathogenic	0.9972	pathogenic	-1.224	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	I
A/L	0.9497	likely_pathogenic	0.9263	pathogenic	0.067	Stabilizing	0.983	D	0.741	deleterious	None	None	None	None	I
A/M	0.9564	likely_pathogenic	0.9383	pathogenic	0.065	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
A/N	0.9815	likely_pathogenic	0.9704	pathogenic	-1.088	Destabilizing	0.995	D	0.75	deleterious	None	None	None	None	I
A/P	0.9893	likely_pathogenic	0.9807	pathogenic	-0.178	Destabilizing	0.997	D	0.791	deleterious	D	0.699369731	None	None	I
A/Q	0.9897	likely_pathogenic	0.9842	pathogenic	-1.08	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	I
A/R	0.9946	likely_pathogenic	0.9902	pathogenic	-1.095	Destabilizing	0.995	D	0.78	deleterious	None	None	None	None	I
A/S	0.2598	likely_benign	0.2296	benign	-1.433	Destabilizing	0.568	D	0.381	neutral	D	0.540958484	None	None	I
A/T	0.7976	likely_pathogenic	0.7275	pathogenic	-1.259	Destabilizing	0.955	D	0.692	prob.neutral	D	0.660173836	None	None	I
A/V	0.9057	likely_pathogenic	0.8676	pathogenic	-0.178	Destabilizing	0.977	D	0.73	prob.delet.	D	0.699369731	None	None	I
A/W	0.9979	likely_pathogenic	0.9962	pathogenic	-1.314	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
A/Y	0.9899	likely_pathogenic	0.9845	pathogenic	-0.785	Destabilizing	1.0	D	0.738	prob.delet.	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.