TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28856	86791;86792;86793	chr2:178559566;178559565;178559564	chr2:179424293;179424292;179424291
N2AB	27215	81868;81869;81870	chr2:178559566;178559565;178559564	chr2:179424293;179424292;179424291
N2A	26288	79087;79088;79089	chr2:178559566;178559565;178559564	chr2:179424293;179424292;179424291
N2B	19791	59596;59597;59598	chr2:178559566;178559565;178559564	chr2:179424293;179424292;179424291
Novex-1	19916	59971;59972;59973	chr2:178559566;178559565;178559564	chr2:179424293;179424292;179424291
Novex-2	19983	60172;60173;60174	chr2:178559566;178559565;178559564	chr2:179424293;179424292;179424291
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-98
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.6493
• 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
D/E	None	None	0.001	N	0.195	0.155	0.146414634003	gnomAD-4.0.0	2.05264E-06	None	None	None	None	N	None	0	4.47187E-05	None	0	0	None	0	0	8.99483E-07	0	0
D/H	rs747235124	0.222	0.931	N	0.613	0.382	0.353125101423	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/H	rs747235124	0.222	0.931	N	0.613	0.382	0.353125101423	gnomAD-4.0.0	1.59132E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85845E-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
D/A	0.1168	likely_benign	0.1017	benign	-0.147	Destabilizing	0.201	N	0.54	neutral	N	0.51268898	None	None	N
D/C	0.468	ambiguous	0.4296	ambiguous	0.049	Stabilizing	0.982	D	0.68	prob.neutral	None	None	None	None	N
D/E	0.087	likely_benign	0.089	benign	-0.303	Destabilizing	0.001	N	0.195	neutral	N	0.43892194	None	None	N
D/F	0.4887	ambiguous	0.4364	ambiguous	-0.128	Destabilizing	0.935	D	0.66	neutral	None	None	None	None	N
D/G	0.1321	likely_benign	0.1119	benign	-0.327	Destabilizing	0.334	N	0.609	neutral	N	0.467925744	None	None	N
D/H	0.2052	likely_benign	0.1786	benign	0.127	Stabilizing	0.931	D	0.613	neutral	N	0.483943312	None	None	N
D/I	0.3168	likely_benign	0.2775	benign	0.273	Stabilizing	0.826	D	0.669	neutral	None	None	None	None	N
D/K	0.2741	likely_benign	0.2359	benign	0.417	Stabilizing	0.25	N	0.578	neutral	None	None	None	None	N
D/L	0.3163	likely_benign	0.2753	benign	0.273	Stabilizing	0.7	D	0.645	neutral	None	None	None	None	N
D/M	0.4163	ambiguous	0.3877	ambiguous	0.299	Stabilizing	0.982	D	0.643	neutral	None	None	None	None	N
D/N	0.0813	likely_benign	0.0751	benign	0.122	Stabilizing	0.334	N	0.591	neutral	N	0.495372656	None	None	N
D/P	0.8246	likely_pathogenic	0.7365	pathogenic	0.155	Stabilizing	0.826	D	0.615	neutral	None	None	None	None	N
D/Q	0.211	likely_benign	0.1937	benign	0.142	Stabilizing	0.539	D	0.562	neutral	None	None	None	None	N
D/R	0.3443	ambiguous	0.2858	benign	0.59	Stabilizing	0.539	D	0.605	neutral	None	None	None	None	N
D/S	0.1031	likely_benign	0.0943	benign	0.029	Stabilizing	0.25	N	0.555	neutral	None	None	None	None	N
D/T	0.1729	likely_benign	0.155	benign	0.168	Stabilizing	0.7	D	0.581	neutral	None	None	None	None	N
D/V	0.1848	likely_benign	0.1611	benign	0.155	Stabilizing	0.638	D	0.633	neutral	N	0.475927915	None	None	N
D/W	0.8108	likely_pathogenic	0.7675	pathogenic	-0.025	Destabilizing	0.982	D	0.672	neutral	None	None	None	None	N
D/Y	0.2092	likely_benign	0.1769	benign	0.11	Stabilizing	0.916	D	0.661	neutral	N	0.469953661	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.