TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30675	92248;92249;92250	chr2:178549699;178549698;178549697	chr2:179414426;179414425;179414424
N2AB	29034	87325;87326;87327	chr2:178549699;178549698;178549697	chr2:179414426;179414425;179414424
N2A	28107	84544;84545;84546	chr2:178549699;178549698;178549697	chr2:179414426;179414425;179414424
N2B	21610	65053;65054;65055	chr2:178549699;178549698;178549697	chr2:179414426;179414425;179414424
Novex-1	21735	65428;65429;65430	chr2:178549699;178549698;178549697	chr2:179414426;179414425;179414424
Novex-2	21802	65629;65630;65631	chr2:178549699;178549698;178549697	chr2:179414426;179414425;179414424
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: Fn3-111
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.9163
• Predicted PPI site: I

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/A	rs765085883	0.037	0.41	N	0.61	0.222	0.322510055762	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/A	rs765085883	0.037	0.41	N	0.61	0.222	0.322510055762	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs765085883	0.037	0.41	N	0.61	0.222	0.322510055762	gnomAD-4.0.0	3.09843E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.23806E-06	0	0
E/K	None	None	0.41	N	0.579	0.186	0.263612267334	gnomAD-4.0.0	1.59138E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85847E-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
E/A	0.1267	likely_benign	0.1257	benign	-0.26	Destabilizing	0.41	N	0.61	neutral	N	0.464127029	None	None	I
E/C	0.7699	likely_pathogenic	0.7558	pathogenic	-0.122	Destabilizing	0.993	D	0.714	prob.delet.	None	None	None	None	I
E/D	0.1125	likely_benign	0.1127	benign	-0.316	Destabilizing	0.581	D	0.495	neutral	N	0.472591796	None	None	I
E/F	0.6331	likely_pathogenic	0.6403	pathogenic	-0.147	Destabilizing	0.993	D	0.677	prob.neutral	None	None	None	None	I
E/G	0.1469	likely_benign	0.1461	benign	-0.44	Destabilizing	0.83	D	0.562	neutral	N	0.473170587	None	None	I
E/H	0.3633	ambiguous	0.3526	ambiguous	0.229	Stabilizing	0.961	D	0.753	deleterious	None	None	None	None	I
E/I	0.2518	likely_benign	0.2492	benign	0.174	Stabilizing	0.929	D	0.682	prob.neutral	None	None	None	None	I
E/K	0.1037	likely_benign	0.1075	benign	0.333	Stabilizing	0.41	N	0.579	neutral	N	0.409428539	None	None	I
E/L	0.2649	likely_benign	0.2514	benign	0.174	Stabilizing	0.866	D	0.64	neutral	None	None	None	None	I
E/M	0.3436	ambiguous	0.3342	benign	0.124	Stabilizing	0.98	D	0.651	neutral	None	None	None	None	I
E/N	0.2025	likely_benign	0.1981	benign	0.013	Stabilizing	0.866	D	0.71	prob.delet.	None	None	None	None	I
E/P	0.3027	likely_benign	0.2798	benign	0.049	Stabilizing	0.929	D	0.693	prob.neutral	None	None	None	None	I
E/Q	0.1235	likely_benign	0.1146	benign	0.049	Stabilizing	0.01	N	0.283	neutral	N	0.430379815	None	None	I
E/R	0.1964	likely_benign	0.1973	benign	0.583	Stabilizing	0.764	D	0.711	prob.delet.	None	None	None	None	I
E/S	0.1608	likely_benign	0.1541	benign	-0.139	Destabilizing	0.48	N	0.63	neutral	None	None	None	None	I
E/T	0.1583	likely_benign	0.1535	benign	0.011	Stabilizing	0.866	D	0.661	neutral	None	None	None	None	I
E/V	0.1517	likely_benign	0.1524	benign	0.049	Stabilizing	0.83	D	0.629	neutral	N	0.480019201	None	None	I
E/W	0.8367	likely_pathogenic	0.8386	pathogenic	-0.019	Destabilizing	0.993	D	0.716	prob.delet.	None	None	None	None	I
E/Y	0.5333	ambiguous	0.5287	ambiguous	0.092	Stabilizing	0.929	D	0.671	neutral	None	None	None	None	I

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.