TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15105	45538;45539;45540	chr2:178621511;178621510;178621509	chr2:179486238;179486237;179486236
N2AB	13464	40615;40616;40617	chr2:178621511;178621510;178621509	chr2:179486238;179486237;179486236
N2A	12537	37834;37835;37836	chr2:178621511;178621510;178621509	chr2:179486238;179486237;179486236
N2B	6040	18343;18344;18345	chr2:178621511;178621510;178621509	chr2:179486238;179486237;179486236
Novex-1	6165	18718;18719;18720	chr2:178621511;178621510;178621509	chr2:179486238;179486237;179486236
Novex-2	6232	18919;18920;18921	chr2:178621511;178621510;178621509	chr2:179486238;179486237;179486236
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-102
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.543
• 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
P/R	None	None	0.999	N	0.799	0.363	0.655515966292	gnomAD-4.0.0	1.59408E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86307E-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
P/A	0.1304	likely_benign	0.1037	benign	-0.324	Destabilizing	0.992	D	0.569	neutral	N	0.50425116	None	None	N
P/C	0.7346	likely_pathogenic	0.6528	pathogenic	-0.824	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/D	0.5265	ambiguous	0.4256	ambiguous	-0.118	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
P/E	0.368	ambiguous	0.2946	benign	-0.226	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
P/F	0.5985	likely_pathogenic	0.479	ambiguous	-0.641	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/G	0.3774	ambiguous	0.3277	benign	-0.39	Destabilizing	0.997	D	0.721	prob.delet.	None	None	None	None	N
P/H	0.2775	likely_benign	0.202	benign	0.021	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
P/I	0.4518	ambiguous	0.3499	ambiguous	-0.291	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/K	0.3838	ambiguous	0.3039	benign	-0.331	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
P/L	0.1832	likely_benign	0.1387	benign	-0.291	Destabilizing	0.999	D	0.761	deleterious	N	0.505401267	None	None	N
P/M	0.4699	ambiguous	0.3863	ambiguous	-0.551	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/N	0.4372	ambiguous	0.3553	ambiguous	-0.17	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
P/Q	0.2245	likely_benign	0.1731	benign	-0.348	Destabilizing	0.999	D	0.757	deleterious	N	0.505256611	None	None	N
P/R	0.2439	likely_benign	0.1815	benign	0.074	Stabilizing	0.999	D	0.799	deleterious	N	0.490438205	None	None	N
P/S	0.1649	likely_benign	0.1257	benign	-0.518	Destabilizing	0.957	D	0.415	neutral	N	0.487296851	None	None	N
P/T	0.1685	likely_benign	0.1253	benign	-0.53	Destabilizing	0.999	D	0.727	prob.delet.	N	0.48590916	None	None	N
P/V	0.3335	likely_benign	0.2656	benign	-0.274	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
P/W	0.7458	likely_pathogenic	0.6486	pathogenic	-0.699	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/Y	0.5456	ambiguous	0.4291	ambiguous	-0.427	Destabilizing	1.0	D	0.791	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.