TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7862	23809;23810;23811	chr2:178720058;178720057;178720056	chr2:179584785;179584784;179584783
N2AB	7545	22858;22859;22860	chr2:178720058;178720057;178720056	chr2:179584785;179584784;179584783
N2A	6618	20077;20078;20079	chr2:178720058;178720057;178720056	chr2:179584785;179584784;179584783
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-63
• Domain position: 68
• Structural Position: 149
• Q(SASA): 0.2343
• 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/T	rs794729629	-0.543	0.006	N	0.458	0.203	0.344945010812	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/T	rs794729629	-0.543	0.006	N	0.458	0.203	0.344945010812	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.2055	likely_benign	0.1669	benign	-1.057	Destabilizing	0.001	N	0.518	neutral	None	None	None	None	N
N/C	0.2374	likely_benign	0.1953	benign	-0.194	Destabilizing	0.882	D	0.714	prob.delet.	None	None	None	None	N
N/D	0.0936	likely_benign	0.1014	benign	-0.374	Destabilizing	None	N	0.239	neutral	N	0.348560934	None	None	N
N/E	0.4097	ambiguous	0.3837	ambiguous	-0.246	Destabilizing	None	N	0.243	neutral	None	None	None	None	N
N/F	0.456	ambiguous	0.3927	ambiguous	-0.908	Destabilizing	0.699	D	0.731	prob.delet.	None	None	None	None	N
N/G	0.2673	likely_benign	0.2199	benign	-1.404	Destabilizing	0.019	N	0.455	neutral	None	None	None	None	N
N/H	0.0792	likely_benign	0.0882	benign	-0.963	Destabilizing	None	N	0.367	neutral	N	0.454945477	None	None	N
N/I	0.2307	likely_benign	0.1972	benign	-0.165	Destabilizing	0.157	N	0.719	prob.delet.	N	0.500571489	None	None	N
N/K	0.4333	ambiguous	0.3939	ambiguous	-0.088	Destabilizing	0.001	N	0.278	neutral	N	0.51133191	None	None	N
N/L	0.236	likely_benign	0.2084	benign	-0.165	Destabilizing	0.048	N	0.627	neutral	None	None	None	None	N
N/M	0.3534	ambiguous	0.3102	benign	0.234	Stabilizing	0.465	N	0.714	prob.delet.	None	None	None	None	N
N/P	0.7356	likely_pathogenic	0.6819	pathogenic	-0.434	Destabilizing	0.051	N	0.663	neutral	None	None	None	None	N
N/Q	0.3275	likely_benign	0.3095	benign	-0.777	Destabilizing	None	N	0.334	neutral	None	None	None	None	N
N/R	0.4311	ambiguous	0.3917	ambiguous	-0.104	Destabilizing	0.063	N	0.472	neutral	None	None	None	None	N
N/S	0.068	likely_benign	0.0602	benign	-0.978	Destabilizing	None	N	0.283	neutral	N	0.4968881	None	None	N
N/T	0.1383	likely_benign	0.1328	benign	-0.627	Destabilizing	0.006	N	0.458	neutral	N	0.485087353	None	None	N
N/V	0.221	likely_benign	0.1878	benign	-0.434	Destabilizing	0.01	N	0.636	neutral	None	None	None	None	N
N/W	0.734	likely_pathogenic	0.6909	pathogenic	-0.629	Destabilizing	0.964	D	0.715	prob.delet.	None	None	None	None	N
N/Y	0.152	likely_benign	0.145	benign	-0.413	Destabilizing	0.11	N	0.707	prob.neutral	N	0.500317999	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.