TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8194	24805;24806;24807	chr2:178718526;178718525;178718524	chr2:179583253;179583252;179583251
N2AB	7877	23854;23855;23856	chr2:178718526;178718525;178718524	chr2:179583253;179583252;179583251
N2A	6950	21073;21074;21075	chr2:178718526;178718525;178718524	chr2:179583253;179583252;179583251
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-67
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1211
• 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	rs763264570	-1.74	0.295	N	0.647	0.307	0.31291088546	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Y/H	rs763264570	-1.74	0.295	N	0.647	0.307	0.31291088546	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85848E-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	0.8786	likely_pathogenic	0.8866	pathogenic	-2.751	Highly Destabilizing	0.016	N	0.585	neutral	None	None	None	None	N
Y/C	0.2993	likely_benign	0.2958	benign	-1.734	Destabilizing	None	N	0.495	neutral	N	0.504619959	None	None	N
Y/D	0.9747	likely_pathogenic	0.9806	pathogenic	-2.61	Highly Destabilizing	0.171	N	0.788	deleterious	N	0.504619959	None	None	N
Y/E	0.9886	likely_pathogenic	0.991	pathogenic	-2.418	Highly Destabilizing	0.072	N	0.74	deleterious	None	None	None	None	N
Y/F	0.0573	likely_benign	0.07	benign	-0.992	Destabilizing	None	N	0.203	neutral	N	0.457001561	None	None	N
Y/G	0.9051	likely_pathogenic	0.9173	pathogenic	-3.158	Highly Destabilizing	0.072	N	0.728	prob.delet.	None	None	None	None	N
Y/H	0.6782	likely_pathogenic	0.7152	pathogenic	-1.779	Destabilizing	0.295	N	0.647	neutral	N	0.515976264	None	None	N
Y/I	0.6813	likely_pathogenic	0.6938	pathogenic	-1.428	Destabilizing	0.038	N	0.623	neutral	None	None	None	None	N
Y/K	0.9803	likely_pathogenic	0.9828	pathogenic	-1.732	Destabilizing	0.072	N	0.737	prob.delet.	None	None	None	None	N
Y/L	0.7836	likely_pathogenic	0.7841	pathogenic	-1.428	Destabilizing	0.016	N	0.507	neutral	None	None	None	None	N
Y/M	0.8386	likely_pathogenic	0.8518	pathogenic	-1.331	Destabilizing	0.356	N	0.737	prob.delet.	None	None	None	None	N
Y/N	0.8831	likely_pathogenic	0.9074	pathogenic	-2.395	Highly Destabilizing	0.171	N	0.777	deleterious	N	0.515976264	None	None	N
Y/P	0.9905	likely_pathogenic	0.9914	pathogenic	-1.879	Destabilizing	0.628	D	0.805	deleterious	None	None	None	None	N
Y/Q	0.9661	likely_pathogenic	0.972	pathogenic	-2.183	Highly Destabilizing	0.356	N	0.74	deleterious	None	None	None	None	N
Y/R	0.9464	likely_pathogenic	0.9486	pathogenic	-1.496	Destabilizing	0.356	N	0.775	deleterious	None	None	None	None	N
Y/S	0.8052	likely_pathogenic	0.8295	pathogenic	-2.876	Highly Destabilizing	0.002	N	0.478	neutral	D	0.52711222	None	None	N
Y/T	0.9018	likely_pathogenic	0.9143	pathogenic	-2.563	Highly Destabilizing	0.072	N	0.677	prob.neutral	None	None	None	None	N
Y/V	0.5636	ambiguous	0.5571	ambiguous	-1.879	Destabilizing	0.001	N	0.397	neutral	None	None	None	None	N
Y/W	0.448	ambiguous	0.4723	ambiguous	-0.328	Destabilizing	0.356	N	0.638	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.