TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8124	24595;24596;24597	chr2:178718830;178718829;178718828	chr2:179583557;179583556;179583555
N2AB	7807	23644;23645;23646	chr2:178718830;178718829;178718828	chr2:179583557;179583556;179583555
N2A	6880	20863;20864;20865	chr2:178718830;178718829;178718828	chr2:179583557;179583556;179583555
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-66
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1462
• 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
C/R	rs1577966478	None	0.999	N	0.735	0.604	0.854177468779	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.4108E-04	0	0	0
C/Y	rs754319631	-1.527	0.4	N	0.429	0.317	0.651574910104	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
C/Y	rs754319631	-1.527	0.4	N	0.429	0.317	0.651574910104	gnomAD-4.0.0	7.52636E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89431E-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
C/A	0.4563	ambiguous	0.4674	ambiguous	-1.796	Destabilizing	0.982	D	0.577	neutral	None	None	None	None	N
C/D	0.823	likely_pathogenic	0.8315	pathogenic	-0.419	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
C/E	0.8135	likely_pathogenic	0.8269	pathogenic	-0.264	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
C/F	0.2167	likely_benign	0.2233	benign	-1.114	Destabilizing	0.961	D	0.644	neutral	N	0.48480145	None	None	N
C/G	0.2306	likely_benign	0.2449	benign	-2.139	Highly Destabilizing	0.997	D	0.673	neutral	D	0.525226708	None	None	N
C/H	0.4325	ambiguous	0.4324	ambiguous	-2.174	Highly Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
C/I	0.4844	ambiguous	0.5023	ambiguous	-0.894	Destabilizing	0.993	D	0.626	neutral	None	None	None	None	N
C/K	0.7228	likely_pathogenic	0.7337	pathogenic	-0.879	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
C/L	0.4971	ambiguous	0.5136	ambiguous	-0.894	Destabilizing	0.964	D	0.609	neutral	None	None	None	None	N
C/M	0.6545	likely_pathogenic	0.6773	pathogenic	0.009	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	N
C/N	0.6197	likely_pathogenic	0.6118	pathogenic	-1.06	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
C/P	0.949	likely_pathogenic	0.9495	pathogenic	-1.169	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
C/Q	0.5513	ambiguous	0.5655	pathogenic	-0.825	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
C/R	0.3004	likely_benign	0.3131	benign	-0.978	Destabilizing	0.999	D	0.735	prob.delet.	N	0.509238535	None	None	N
C/S	0.3203	likely_benign	0.3213	benign	-1.596	Destabilizing	0.99	D	0.629	neutral	N	0.518762095	None	None	N
C/T	0.4677	ambiguous	0.4654	ambiguous	-1.239	Destabilizing	0.993	D	0.626	neutral	None	None	None	None	N
C/V	0.4186	ambiguous	0.4285	ambiguous	-1.169	Destabilizing	0.985	D	0.601	neutral	None	None	None	None	N
C/W	0.3787	ambiguous	0.4018	ambiguous	-1.185	Destabilizing	1.0	D	0.669	neutral	N	0.486035178	None	None	N
C/Y	0.251	likely_benign	0.2496	benign	-1.126	Destabilizing	0.4	N	0.429	neutral	N	0.438586371	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.