TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25167	75724;75725;75726	chr2:178570633;178570632;178570631	chr2:179435360;179435359;179435358
N2AB	23526	70801;70802;70803	chr2:178570633;178570632;178570631	chr2:179435360;179435359;179435358
N2A	22599	68020;68021;68022	chr2:178570633;178570632;178570631	chr2:179435360;179435359;179435358
N2B	16102	48529;48530;48531	chr2:178570633;178570632;178570631	chr2:179435360;179435359;179435358
Novex-1	16227	48904;48905;48906	chr2:178570633;178570632;178570631	chr2:179435360;179435359;179435358
Novex-2	16294	49105;49106;49107	chr2:178570633;178570632;178570631	chr2:179435360;179435359;179435358
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-134
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.1168
• 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
T/I	rs1396100350	0.515	0.97	N	0.718	0.479	0.304760801415	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
T/I	rs1396100350	0.515	0.97	N	0.718	0.479	0.304760801415	gnomAD-4.0.0	2.05299E-06	None	None	None	None	N	None	2.99007E-05	0	None	0	0	None	0	0	0	2.31889E-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
T/A	0.087	likely_benign	0.0873	benign	-1.309	Destabilizing	0.025	N	0.465	neutral	N	0.448434353	None	None	N
T/C	0.4215	ambiguous	0.4264	ambiguous	-1.054	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
T/D	0.9176	likely_pathogenic	0.9411	pathogenic	-1.412	Destabilizing	0.956	D	0.723	prob.delet.	None	None	None	None	N
T/E	0.9049	likely_pathogenic	0.9384	pathogenic	-1.22	Destabilizing	0.86	D	0.71	prob.delet.	None	None	None	None	N
T/F	0.6662	likely_pathogenic	0.7322	pathogenic	-1.25	Destabilizing	0.978	D	0.715	prob.delet.	None	None	None	None	N
T/G	0.5025	ambiguous	0.5373	ambiguous	-1.713	Destabilizing	0.754	D	0.696	prob.neutral	None	None	None	None	N
T/H	0.7604	likely_pathogenic	0.8113	pathogenic	-1.9	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
T/I	0.5141	ambiguous	0.5653	pathogenic	-0.248	Destabilizing	0.97	D	0.718	prob.delet.	N	0.479543587	None	None	N
T/K	0.8985	likely_pathogenic	0.936	pathogenic	-0.507	Destabilizing	0.86	D	0.713	prob.delet.	None	None	None	None	N
T/L	0.3078	likely_benign	0.3359	benign	-0.248	Destabilizing	0.86	D	0.684	prob.neutral	None	None	None	None	N
T/M	0.1974	likely_benign	0.2117	benign	-0.088	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
T/N	0.5564	ambiguous	0.6139	pathogenic	-1.252	Destabilizing	0.942	D	0.753	deleterious	N	0.45793384	None	None	N
T/P	0.9083	likely_pathogenic	0.9308	pathogenic	-0.571	Destabilizing	0.97	D	0.708	prob.delet.	N	0.487140911	None	None	N
T/Q	0.8033	likely_pathogenic	0.8519	pathogenic	-1.063	Destabilizing	0.956	D	0.717	prob.delet.	None	None	None	None	N
T/R	0.8434	likely_pathogenic	0.8978	pathogenic	-0.708	Destabilizing	0.956	D	0.716	prob.delet.	None	None	None	None	N
T/S	0.1673	likely_benign	0.1743	benign	-1.54	Destabilizing	0.058	N	0.527	neutral	N	0.445490048	None	None	N
T/V	0.2508	likely_benign	0.2817	benign	-0.571	Destabilizing	0.86	D	0.68	prob.neutral	None	None	None	None	N
T/W	0.955	likely_pathogenic	0.9706	pathogenic	-1.315	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.7692	likely_pathogenic	0.8293	pathogenic	-0.951	Destabilizing	0.993	D	0.719	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.