TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1095	3508;3509;3510	chr2:178782309;178782308;178782307	chr2:179647036;179647035;179647034
N2AB	1095	3508;3509;3510	chr2:178782309;178782308;178782307	chr2:179647036;179647035;179647034
N2A	1095	3508;3509;3510	chr2:178782309;178782308;178782307	chr2:179647036;179647035;179647034
N2B	1049	3370;3371;3372	chr2:178782309;178782308;178782307	chr2:179647036;179647035;179647034
Novex-1	1049	3370;3371;3372	chr2:178782309;178782308;178782307	chr2:179647036;179647035;179647034
Novex-2	1049	3370;3371;3372	chr2:178782309;178782308;178782307	chr2:179647036;179647035;179647034
Novex-3	1095	3508;3509;3510	chr2:178782309;178782308;178782307	chr2:179647036;179647035;179647034

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-4
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.6681
• 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/D	rs372103803	None	0.999	N	0.444	0.221	0.266843984389	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/D	rs372103803	None	0.999	N	0.444	0.221	0.266843984389	gnomAD-4.0.0	7.43491E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.47456E-06	0	3.20082E-05

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	0.3627	ambiguous	0.4059	ambiguous	-0.588	Destabilizing	0.999	D	0.632	neutral	N	0.452808236	None	None	I
E/C	0.9808	likely_pathogenic	0.983	pathogenic	-0.312	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
E/D	0.4892	ambiguous	0.4935	ambiguous	-0.373	Destabilizing	0.999	D	0.444	neutral	N	0.453320328	None	None	I
E/F	0.974	likely_pathogenic	0.9767	pathogenic	-0.137	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/G	0.5512	ambiguous	0.5865	pathogenic	-0.824	Destabilizing	1.0	D	0.659	neutral	D	0.620874159	None	None	I
E/H	0.89	likely_pathogenic	0.9006	pathogenic	0.156	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	I
E/I	0.8193	likely_pathogenic	0.8367	pathogenic	0.021	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
E/K	0.436	ambiguous	0.4775	ambiguous	0.216	Stabilizing	0.999	D	0.607	neutral	N	0.482996606	None	None	I
E/L	0.8221	likely_pathogenic	0.8304	pathogenic	0.021	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/M	0.8628	likely_pathogenic	0.8806	pathogenic	0.079	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/N	0.7343	likely_pathogenic	0.7626	pathogenic	-0.381	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/P	0.7016	likely_pathogenic	0.7248	pathogenic	-0.163	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
E/Q	0.3969	ambiguous	0.4284	ambiguous	-0.285	Destabilizing	1.0	D	0.627	neutral	N	0.462146957	None	None	I
E/R	0.6161	likely_pathogenic	0.649	pathogenic	0.529	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
E/S	0.5146	ambiguous	0.5522	ambiguous	-0.524	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
E/T	0.6239	likely_pathogenic	0.663	pathogenic	-0.311	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/V	0.6097	likely_pathogenic	0.6437	pathogenic	-0.163	Destabilizing	1.0	D	0.72	prob.delet.	N	0.455045563	None	None	I
E/W	0.9918	likely_pathogenic	0.9925	pathogenic	0.143	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
E/Y	0.9513	likely_pathogenic	0.956	pathogenic	0.133	Stabilizing	1.0	D	0.711	prob.delet.	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.