TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22025	66298;66299;66300	chr2:178582383;178582382;178582381	chr2:179447110;179447109;179447108
N2AB	20384	61375;61376;61377	chr2:178582383;178582382;178582381	chr2:179447110;179447109;179447108
N2A	19457	58594;58595;58596	chr2:178582383;178582382;178582381	chr2:179447110;179447109;179447108
N2B	12960	39103;39104;39105	chr2:178582383;178582382;178582381	chr2:179447110;179447109;179447108
Novex-1	13085	39478;39479;39480	chr2:178582383;178582382;178582381	chr2:179447110;179447109;179447108
Novex-2	13152	39679;39680;39681	chr2:178582383;178582382;178582381	chr2:179447110;179447109;179447108
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-47
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.3966
• 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	rs772896091	-0.436	0.999	N	0.607	0.312	0.406945738958	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs772896091	-0.436	0.999	N	0.607	0.312	0.406945738958	gnomAD-4.0.0	3.18683E-06	None	None	None	None	N	None	0	2.28938E-05	None	0	0	None	0	0	2.86134E-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	0.5721	likely_pathogenic	0.458	ambiguous	-0.988	Destabilizing	0.999	D	0.709	prob.delet.	N	0.491830124	None	None	N
E/C	0.9695	likely_pathogenic	0.9583	pathogenic	-0.486	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/D	0.832	likely_pathogenic	0.7733	pathogenic	-1.128	Destabilizing	0.999	D	0.47	neutral	N	0.4855627	None	None	N
E/F	0.9863	likely_pathogenic	0.9778	pathogenic	-0.363	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/G	0.81	likely_pathogenic	0.7253	pathogenic	-1.379	Destabilizing	1.0	D	0.764	deleterious	N	0.496540612	None	None	N
E/H	0.94	likely_pathogenic	0.9009	pathogenic	-0.633	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/I	0.799	likely_pathogenic	0.7594	pathogenic	0.092	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/K	0.6663	likely_pathogenic	0.5746	pathogenic	-0.646	Destabilizing	0.999	D	0.607	neutral	N	0.480256328	None	None	N
E/L	0.8979	likely_pathogenic	0.855	pathogenic	0.092	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/M	0.8704	likely_pathogenic	0.82	pathogenic	0.6	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/N	0.8733	likely_pathogenic	0.8087	pathogenic	-1.156	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/P	0.976	likely_pathogenic	0.9564	pathogenic	-0.247	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Q	0.37	ambiguous	0.2947	benign	-1.002	Destabilizing	1.0	D	0.615	neutral	N	0.521809895	None	None	N
E/R	0.7724	likely_pathogenic	0.7088	pathogenic	-0.373	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/S	0.6927	likely_pathogenic	0.5952	pathogenic	-1.524	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
E/T	0.6572	likely_pathogenic	0.5848	pathogenic	-1.191	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/V	0.6486	likely_pathogenic	0.5941	pathogenic	-0.247	Destabilizing	1.0	D	0.797	deleterious	N	0.474081491	None	None	N
E/W	0.9964	likely_pathogenic	0.9949	pathogenic	-0.079	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/Y	0.9782	likely_pathogenic	0.965	pathogenic	-0.089	Destabilizing	1.0	D	0.772	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.