TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15076	45451;45452;45453	chr2:178621598;178621597;178621596	chr2:179486325;179486324;179486323
N2AB	13435	40528;40529;40530	chr2:178621598;178621597;178621596	chr2:179486325;179486324;179486323
N2A	12508	37747;37748;37749	chr2:178621598;178621597;178621596	chr2:179486325;179486324;179486323
N2B	6011	18256;18257;18258	chr2:178621598;178621597;178621596	chr2:179486325;179486324;179486323
Novex-1	6136	18631;18632;18633	chr2:178621598;178621597;178621596	chr2:179486325;179486324;179486323
Novex-2	6203	18832;18833;18834	chr2:178621598;178621597;178621596	chr2:179486325;179486324;179486323
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-102
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.2549
• 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
Y/H	None	None	0.916	N	0.621	0.425	0.443797312901	gnomAD-4.0.0	1.36932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79984E-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
Y/A	0.7861	likely_pathogenic	0.6825	pathogenic	-2.91	Highly Destabilizing	0.399	N	0.618	neutral	None	None	None	None	N
Y/C	0.2108	likely_benign	0.1669	benign	-1.82	Destabilizing	0.976	D	0.719	prob.delet.	D	0.697559508	None	None	N
Y/D	0.7471	likely_pathogenic	0.5715	pathogenic	-2.6	Highly Destabilizing	0.916	D	0.771	deleterious	D	0.698014229	None	None	N
Y/E	0.8689	likely_pathogenic	0.7654	pathogenic	-2.427	Highly Destabilizing	0.826	D	0.723	prob.delet.	None	None	None	None	N
Y/F	0.1351	likely_benign	0.0858	benign	-1.072	Destabilizing	0.002	N	0.227	neutral	N	0.501725664	None	None	N
Y/G	0.7109	likely_pathogenic	0.6426	pathogenic	-3.32	Highly Destabilizing	0.826	D	0.75	deleterious	None	None	None	None	N
Y/H	0.3528	ambiguous	0.2432	benign	-1.793	Destabilizing	0.916	D	0.621	neutral	N	0.514569717	None	None	N
Y/I	0.6498	likely_pathogenic	0.4935	ambiguous	-1.584	Destabilizing	0.539	D	0.674	neutral	None	None	None	None	N
Y/K	0.7919	likely_pathogenic	0.6998	pathogenic	-2.126	Highly Destabilizing	0.826	D	0.72	prob.delet.	None	None	None	None	N
Y/L	0.6611	likely_pathogenic	0.5954	pathogenic	-1.584	Destabilizing	0.25	N	0.545	neutral	None	None	None	None	N
Y/M	0.7402	likely_pathogenic	0.6328	pathogenic	-1.331	Destabilizing	0.947	D	0.691	prob.neutral	None	None	None	None	N
Y/N	0.4454	ambiguous	0.2986	benign	-2.767	Highly Destabilizing	0.916	D	0.749	deleterious	D	0.697651335	None	None	N
Y/P	0.9678	likely_pathogenic	0.9561	pathogenic	-2.034	Highly Destabilizing	0.935	D	0.771	deleterious	None	None	None	None	N
Y/Q	0.7592	likely_pathogenic	0.6213	pathogenic	-2.548	Highly Destabilizing	0.935	D	0.729	prob.delet.	None	None	None	None	N
Y/R	0.6569	likely_pathogenic	0.5572	ambiguous	-1.81	Destabilizing	0.826	D	0.752	deleterious	None	None	None	None	N
Y/S	0.5504	ambiguous	0.3942	ambiguous	-3.223	Highly Destabilizing	0.781	D	0.721	prob.delet.	D	0.657870536	None	None	N
Y/T	0.6862	likely_pathogenic	0.5349	ambiguous	-2.933	Highly Destabilizing	0.826	D	0.723	prob.delet.	None	None	None	None	N
Y/V	0.5476	ambiguous	0.4222	ambiguous	-2.034	Highly Destabilizing	0.25	N	0.617	neutral	None	None	None	None	N
Y/W	0.4742	ambiguous	0.3727	ambiguous	-0.477	Destabilizing	0.947	D	0.608	neutral	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.