TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16633	50122;50123;50124	chr2:178612824;178612823;178612822	chr2:179477551;179477550;179477549
N2AB	14992	45199;45200;45201	chr2:178612824;178612823;178612822	chr2:179477551;179477550;179477549
N2A	14065	42418;42419;42420	chr2:178612824;178612823;178612822	chr2:179477551;179477550;179477549
N2B	7568	22927;22928;22929	chr2:178612824;178612823;178612822	chr2:179477551;179477550;179477549
Novex-1	7693	23302;23303;23304	chr2:178612824;178612823;178612822	chr2:179477551;179477550;179477549
Novex-2	7760	23503;23504;23505	chr2:178612824;178612823;178612822	chr2:179477551;179477550;179477549
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: Fn3-8
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.4687
• 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	None	None	0.939	N	0.726	0.232	0.341226946553	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.259	likely_benign	0.302	benign	-0.807	Destabilizing	0.885	D	0.681	prob.neutral	N	0.479356471	None	None	N
E/C	0.9324	likely_pathogenic	0.9448	pathogenic	-0.175	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
E/D	0.4102	ambiguous	0.3943	ambiguous	-0.678	Destabilizing	0.939	D	0.605	neutral	N	0.484877593	None	None	N
E/F	0.8585	likely_pathogenic	0.879	pathogenic	-0.548	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
E/G	0.4935	ambiguous	0.592	pathogenic	-1.066	Destabilizing	0.046	N	0.513	neutral	N	0.474837397	None	None	N
E/H	0.838	likely_pathogenic	0.8745	pathogenic	-0.575	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
E/I	0.4718	ambiguous	0.4692	ambiguous	-0.132	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
E/K	0.4782	ambiguous	0.5932	pathogenic	0.04	Stabilizing	0.939	D	0.726	prob.delet.	N	0.477137354	None	None	N
E/L	0.6018	likely_pathogenic	0.6067	pathogenic	-0.132	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
E/M	0.6464	likely_pathogenic	0.6616	pathogenic	0.242	Stabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
E/N	0.6898	likely_pathogenic	0.7093	pathogenic	-0.396	Destabilizing	0.986	D	0.778	deleterious	None	None	None	None	N
E/P	0.6492	likely_pathogenic	0.6578	pathogenic	-0.337	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
E/Q	0.3481	ambiguous	0.4016	ambiguous	-0.356	Destabilizing	0.997	D	0.745	deleterious	N	0.460714444	None	None	N
E/R	0.6827	likely_pathogenic	0.7675	pathogenic	0.222	Stabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
E/S	0.4904	ambiguous	0.5406	ambiguous	-0.6	Destabilizing	0.953	D	0.724	prob.delet.	None	None	None	None	N
E/T	0.4875	ambiguous	0.5271	ambiguous	-0.381	Destabilizing	0.993	D	0.738	prob.delet.	None	None	None	None	N
E/V	0.3042	likely_benign	0.3234	benign	-0.337	Destabilizing	0.991	D	0.806	deleterious	N	0.474774201	None	None	N
E/W	0.9695	likely_pathogenic	0.9786	pathogenic	-0.292	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
E/Y	0.8409	likely_pathogenic	0.8714	pathogenic	-0.274	Destabilizing	0.998	D	0.813	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.