TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9095	27508;27509;27510	chr2:178712742;178712741;178712740	chr2:179577469;179577468;179577467
N2AB	8778	26557;26558;26559	chr2:178712742;178712741;178712740	chr2:179577469;179577468;179577467
N2A	7851	23776;23777;23778	chr2:178712742;178712741;178712740	chr2:179577469;179577468;179577467
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-76
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1637
• 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
N/D	None	None	0.999	D	0.614	0.56	0.287603790349	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/S	rs1319823465	-1.028	0.999	N	0.577	0.51	0.215109475489	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-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
N/A	0.9577	likely_pathogenic	0.9568	pathogenic	-0.986	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
N/C	0.9124	likely_pathogenic	0.8899	pathogenic	-0.258	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
N/D	0.8665	likely_pathogenic	0.8954	pathogenic	-1.149	Destabilizing	0.999	D	0.614	neutral	D	0.535306789	None	None	N
N/E	0.9902	likely_pathogenic	0.9904	pathogenic	-1.033	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
N/F	0.9983	likely_pathogenic	0.9984	pathogenic	-0.744	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
N/G	0.8815	likely_pathogenic	0.8837	pathogenic	-1.325	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	N
N/H	0.8924	likely_pathogenic	0.8965	pathogenic	-1.039	Destabilizing	1.0	D	0.756	deleterious	D	0.547930542	None	None	N
N/I	0.9828	likely_pathogenic	0.9833	pathogenic	-0.116	Destabilizing	1.0	D	0.705	prob.neutral	D	0.559704921	None	None	N
N/K	0.9917	likely_pathogenic	0.9927	pathogenic	-0.31	Destabilizing	1.0	D	0.751	deleterious	D	0.558944453	None	None	N
N/L	0.9589	likely_pathogenic	0.9572	pathogenic	-0.116	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
N/M	0.979	likely_pathogenic	0.9779	pathogenic	0.366	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
N/P	0.9874	likely_pathogenic	0.9865	pathogenic	-0.377	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
N/Q	0.9883	likely_pathogenic	0.989	pathogenic	-1.045	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
N/R	0.9874	likely_pathogenic	0.9877	pathogenic	-0.301	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
N/S	0.2821	likely_benign	0.2866	benign	-1.019	Destabilizing	0.999	D	0.577	neutral	N	0.501046836	None	None	N
N/T	0.7656	likely_pathogenic	0.7623	pathogenic	-0.719	Destabilizing	0.999	D	0.723	prob.delet.	D	0.535560279	None	None	N
N/V	0.9649	likely_pathogenic	0.963	pathogenic	-0.377	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
N/W	0.999	likely_pathogenic	0.9989	pathogenic	-0.491	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
N/Y	0.9803	likely_pathogenic	0.9812	pathogenic	-0.253	Destabilizing	1.0	D	0.737	prob.delet.	D	0.559451432	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.