TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31181	93766;93767;93768	chr2:178548085;178548084;178548083	chr2:179412812;179412811;179412810
N2AB	29540	88843;88844;88845	chr2:178548085;178548084;178548083	chr2:179412812;179412811;179412810
N2A	28613	86062;86063;86064	chr2:178548085;178548084;178548083	chr2:179412812;179412811;179412810
N2B	22116	66571;66572;66573	chr2:178548085;178548084;178548083	chr2:179412812;179412811;179412810
Novex-1	22241	66946;66947;66948	chr2:178548085;178548084;178548083	chr2:179412812;179412811;179412810
Novex-2	22308	67147;67148;67149	chr2:178548085;178548084;178548083	chr2:179412812;179412811;179412810
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-115
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.3358
• 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
E/K	rs1243301263	-0.569	0.999	N	0.613	0.408	0.36036328697	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/K	rs1243301263	-0.569	0.999	N	0.613	0.408	0.36036328697	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	None	0	0	0	0	0
E/Q	None	None	1.0	D	0.632	0.336	0.39619538035	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	0	0	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
E/A	0.2273	likely_benign	0.1923	benign	-1.048	Destabilizing	0.999	D	0.699	prob.neutral	N	0.46977585	None	None	N
E/C	0.94	likely_pathogenic	0.9295	pathogenic	-0.57	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/D	0.4884	ambiguous	0.503	ambiguous	-1.263	Destabilizing	0.999	D	0.497	neutral	N	0.472725138	None	None	N
E/F	0.9448	likely_pathogenic	0.9387	pathogenic	-0.364	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/G	0.4624	ambiguous	0.4125	ambiguous	-1.467	Destabilizing	1.0	D	0.744	deleterious	N	0.480082198	None	None	N
E/H	0.8457	likely_pathogenic	0.8174	pathogenic	-0.639	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/I	0.5833	likely_pathogenic	0.5325	ambiguous	0.123	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/K	0.4681	ambiguous	0.3886	ambiguous	-0.827	Destabilizing	0.999	D	0.613	neutral	N	0.508187237	None	None	N
E/L	0.7082	likely_pathogenic	0.6724	pathogenic	0.123	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/M	0.6791	likely_pathogenic	0.6271	pathogenic	0.693	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/N	0.6422	likely_pathogenic	0.6186	pathogenic	-1.338	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.7043	likely_pathogenic	0.6796	pathogenic	-0.247	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Q	0.267	likely_benign	0.2348	benign	-1.156	Destabilizing	1.0	D	0.632	neutral	D	0.522887331	None	None	N
E/R	0.6316	likely_pathogenic	0.5467	ambiguous	-0.566	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/S	0.4078	ambiguous	0.3727	ambiguous	-1.785	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/T	0.3881	ambiguous	0.3467	ambiguous	-1.419	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/V	0.3606	ambiguous	0.3058	benign	-0.247	Destabilizing	1.0	D	0.78	deleterious	N	0.470296055	None	None	N
E/W	0.9832	likely_pathogenic	0.9805	pathogenic	-0.1	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Y	0.9163	likely_pathogenic	0.9083	pathogenic	-0.084	Destabilizing	1.0	D	0.767	deleterious	None	None	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.