TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28879	86860;86861;86862	chr2:178559497;178559496;178559495	chr2:179424224;179424223;179424222
N2AB	27238	81937;81938;81939	chr2:178559497;178559496;178559495	chr2:179424224;179424223;179424222
N2A	26311	79156;79157;79158	chr2:178559497;178559496;178559495	chr2:179424224;179424223;179424222
N2B	19814	59665;59666;59667	chr2:178559497;178559496;178559495	chr2:179424224;179424223;179424222
Novex-1	19939	60040;60041;60042	chr2:178559497;178559496;178559495	chr2:179424224;179424223;179424222
Novex-2	20006	60241;60242;60243	chr2:178559497;178559496;178559495	chr2:179424224;179424223;179424222
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: Fn3-98
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1186
• 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/K	rs1114167328	None	0.156	N	0.423	0.112	0.101711395817	gnomAD-4.0.0	6.84239E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65662E-05
N/S	None	None	0.706	N	0.573	0.135	0.117506650769	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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	0.3626	ambiguous	0.4699	ambiguous	-0.422	Destabilizing	0.504	D	0.692	prob.neutral	None	None	None	None	N
N/C	0.2513	likely_benign	0.332	benign	0.035	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
N/D	0.4447	ambiguous	0.5509	ambiguous	-1.63	Destabilizing	0.826	D	0.596	neutral	N	0.520577744	None	None	N
N/E	0.7385	likely_pathogenic	0.8459	pathogenic	-1.483	Destabilizing	0.913	D	0.601	neutral	None	None	None	None	N
N/F	0.5305	ambiguous	0.6277	pathogenic	-0.193	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
N/G	0.3228	likely_benign	0.3796	ambiguous	-0.78	Destabilizing	0.981	D	0.586	neutral	None	None	None	None	N
N/H	0.116	likely_benign	0.1523	benign	-0.708	Destabilizing	0.138	N	0.42	neutral	N	0.484753017	None	None	N
N/I	0.4693	ambiguous	0.64	pathogenic	0.494	Stabilizing	0.987	D	0.824	deleterious	N	0.483903632	None	None	N
N/K	0.471	ambiguous	0.678	pathogenic	-0.217	Destabilizing	0.156	N	0.423	neutral	N	0.497911529	None	None	N
N/L	0.44	ambiguous	0.5795	pathogenic	0.494	Stabilizing	0.967	D	0.78	deleterious	None	None	None	None	N
N/M	0.438	ambiguous	0.5975	pathogenic	0.909	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
N/P	0.9872	likely_pathogenic	0.991	pathogenic	0.22	Stabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
N/Q	0.4454	ambiguous	0.5965	pathogenic	-0.933	Destabilizing	0.99	D	0.647	neutral	None	None	None	None	N
N/R	0.4866	ambiguous	0.6399	pathogenic	-0.371	Destabilizing	0.975	D	0.622	neutral	None	None	None	None	N
N/S	0.1304	likely_benign	0.157	benign	-0.901	Destabilizing	0.706	D	0.573	neutral	N	0.47878705	None	None	N
N/T	0.249	likely_benign	0.3549	ambiguous	-0.587	Destabilizing	0.089	N	0.419	neutral	N	0.466506939	None	None	N
N/V	0.4631	ambiguous	0.6229	pathogenic	0.22	Stabilizing	0.896	D	0.783	deleterious	None	None	None	None	N
N/W	0.8203	likely_pathogenic	0.8761	pathogenic	-0.19	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
N/Y	0.1614	likely_benign	0.2	benign	0.187	Stabilizing	0.99	D	0.769	deleterious	N	0.504858931	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.