TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24545	73858;73859;73860	chr2:178572499;178572498;178572497	chr2:179437226;179437225;179437224
N2AB	22904	68935;68936;68937	chr2:178572499;178572498;178572497	chr2:179437226;179437225;179437224
N2A	21977	66154;66155;66156	chr2:178572499;178572498;178572497	chr2:179437226;179437225;179437224
N2B	15480	46663;46664;46665	chr2:178572499;178572498;178572497	chr2:179437226;179437225;179437224
Novex-1	15605	47038;47039;47040	chr2:178572499;178572498;178572497	chr2:179437226;179437225;179437224
Novex-2	15672	47239;47240;47241	chr2:178572499;178572498;178572497	chr2:179437226;179437225;179437224
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-66
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.409
• 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
L/P	rs865922152	None	0.323	N	0.393	0.252	0.37262878642	gnomAD-4.0.0	1.36879E-06	None	None	None	None	I	None	2.99079E-05	0	None	0	0	None	0	0	0	0	1.657E-05
L/R	None	None	0.159	N	0.389	0.168	0.33085137897	gnomAD-4.0.0	1.36879E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79924E-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
L/A	0.2783	likely_benign	0.262	benign	-0.529	Destabilizing	0.035	N	0.367	neutral	None	None	None	None	I
L/C	0.559	ambiguous	0.5146	ambiguous	-0.633	Destabilizing	0.879	D	0.316	neutral	None	None	None	None	I
L/D	0.7157	likely_pathogenic	0.7027	pathogenic	-0.022	Destabilizing	None	N	0.287	neutral	None	None	None	None	I
L/E	0.5027	ambiguous	0.4744	ambiguous	-0.111	Destabilizing	0.032	N	0.459	neutral	None	None	None	None	I
L/F	0.1976	likely_benign	0.1956	benign	-0.556	Destabilizing	None	N	0.223	neutral	N	0.444557046	None	None	I
L/G	0.6281	likely_pathogenic	0.5657	pathogenic	-0.684	Destabilizing	0.082	N	0.441	neutral	None	None	None	None	I
L/H	0.2904	likely_benign	0.2808	benign	0.003	Stabilizing	0.694	D	0.334	neutral	N	0.468433984	None	None	I
L/I	0.0681	likely_benign	0.0672	benign	-0.246	Destabilizing	None	N	0.082	neutral	N	0.402806424	None	None	I
L/K	0.4919	ambiguous	0.4906	ambiguous	-0.258	Destabilizing	0.009	N	0.4	neutral	None	None	None	None	I
L/M	0.1131	likely_benign	0.1141	benign	-0.378	Destabilizing	0.036	N	0.346	neutral	None	None	None	None	I
L/N	0.2793	likely_benign	0.2664	benign	-0.07	Destabilizing	0.135	N	0.407	neutral	None	None	None	None	I
L/P	0.7705	likely_pathogenic	0.6899	pathogenic	-0.308	Destabilizing	0.323	N	0.393	neutral	N	0.478130902	None	None	I
L/Q	0.2424	likely_benign	0.2222	benign	-0.271	Destabilizing	0.208	N	0.379	neutral	None	None	None	None	I
L/R	0.3977	ambiguous	0.3714	ambiguous	0.249	Stabilizing	0.159	N	0.389	neutral	N	0.468260625	None	None	I
L/S	0.2996	likely_benign	0.2762	benign	-0.532	Destabilizing	0.082	N	0.443	neutral	None	None	None	None	I
L/T	0.189	likely_benign	0.1762	benign	-0.509	Destabilizing	0.026	N	0.414	neutral	None	None	None	None	I
L/V	0.0939	likely_benign	0.0942	benign	-0.308	Destabilizing	None	N	0.209	neutral	N	0.442767535	None	None	I
L/W	0.391	ambiguous	0.3488	ambiguous	-0.572	Destabilizing	0.915	D	0.338	neutral	None	None	None	None	I
L/Y	0.4063	ambiguous	0.4186	ambiguous	-0.318	Destabilizing	0.007	N	0.381	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.