TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8876	26851;26852;26853	chr2:178714032;178714031;178714030	chr2:179578759;179578758;179578757
N2AB	8559	25900;25901;25902	chr2:178714032;178714031;178714030	chr2:179578759;179578758;179578757
N2A	7632	23119;23120;23121	chr2:178714032;178714031;178714030	chr2:179578759;179578758;179578757
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-74
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.166
• 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/C	rs1307074594	-1.904	1.0	N	0.747	0.524	0.643332317526	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	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	0.7427	likely_pathogenic	0.8436	pathogenic	-2.956	Highly Destabilizing	0.97	D	0.633	neutral	None	None	None	None	N
Y/C	0.2152	likely_benign	0.2827	benign	-1.986	Destabilizing	1.0	D	0.747	deleterious	N	0.496002813	None	None	N
Y/D	0.6758	likely_pathogenic	0.8228	pathogenic	-2.926	Highly Destabilizing	0.994	D	0.809	deleterious	N	0.512309869	None	None	N
Y/E	0.8091	likely_pathogenic	0.8906	pathogenic	-2.723	Highly Destabilizing	0.996	D	0.73	prob.delet.	None	None	None	None	N
Y/F	0.1497	likely_benign	0.176	benign	-1.094	Destabilizing	0.071	N	0.351	neutral	D	0.524111987	None	None	N
Y/G	0.6791	likely_pathogenic	0.7881	pathogenic	-3.391	Highly Destabilizing	0.996	D	0.76	deleterious	None	None	None	None	N
Y/H	0.1894	likely_benign	0.2471	benign	-1.987	Destabilizing	0.998	D	0.65	neutral	N	0.514012423	None	None	N
Y/I	0.5442	ambiguous	0.6727	pathogenic	-1.53	Destabilizing	0.991	D	0.705	prob.neutral	None	None	None	None	N
Y/K	0.7345	likely_pathogenic	0.8061	pathogenic	-2.152	Highly Destabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	N
Y/L	0.5367	ambiguous	0.6626	pathogenic	-1.53	Destabilizing	0.942	D	0.6	neutral	None	None	None	None	N
Y/M	0.6803	likely_pathogenic	0.7869	pathogenic	-1.368	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
Y/N	0.2721	likely_benign	0.3915	ambiguous	-2.902	Highly Destabilizing	0.994	D	0.77	deleterious	N	0.519791834	None	None	N
Y/P	0.9694	likely_pathogenic	0.9826	pathogenic	-2.017	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
Y/Q	0.5877	likely_pathogenic	0.7118	pathogenic	-2.632	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
Y/R	0.5409	ambiguous	0.6231	pathogenic	-1.921	Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
Y/S	0.4536	ambiguous	0.5887	pathogenic	-3.361	Highly Destabilizing	0.925	D	0.686	prob.neutral	N	0.502079199	None	None	N
Y/T	0.5809	likely_pathogenic	0.7123	pathogenic	-3.031	Highly Destabilizing	0.503	D	0.507	neutral	None	None	None	None	N
Y/V	0.4512	ambiguous	0.5774	pathogenic	-2.017	Highly Destabilizing	0.97	D	0.636	neutral	None	None	None	None	N
Y/W	0.459	ambiguous	0.5304	ambiguous	-0.452	Destabilizing	1.0	D	0.655	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.