TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22441	67546;67547;67548	chr2:178579966;178579965;178579964	chr2:179444693;179444692;179444691
N2AB	20800	62623;62624;62625	chr2:178579966;178579965;178579964	chr2:179444693;179444692;179444691
N2A	19873	59842;59843;59844	chr2:178579966;178579965;178579964	chr2:179444693;179444692;179444691
N2B	13376	40351;40352;40353	chr2:178579966;178579965;178579964	chr2:179444693;179444692;179444691
Novex-1	13501	40726;40727;40728	chr2:178579966;178579965;178579964	chr2:179444693;179444692;179444691
Novex-2	13568	40927;40928;40929	chr2:178579966;178579965;178579964	chr2:179444693;179444692;179444691
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: Fn3-50
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.4711
• 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/G	rs201223583	-0.93	0.999	N	0.695	0.533	None	gnomAD-2.1.1	5.24E-05	None	None	None	None	N	None	6.46E-05	2.9E-05	None	0	0	None	0	None	0	8.92E-05	1.66223E-04
E/G	rs201223583	-0.93	0.999	N	0.695	0.533	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.17696E-04	0	0
E/G	rs201223583	-0.93	0.999	N	0.695	0.533	None	gnomAD-4.0.0	1.34525E-04	None	None	None	None	N	None	0	1.66795E-05	None	0	0	None	0	1.64636E-04	1.68718E-04	0	2.56271E-04

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	0.5422	ambiguous	0.5267	ambiguous	-0.494	Destabilizing	0.997	D	0.776	deleterious	N	0.481062341	None	None	N
E/C	0.9552	likely_pathogenic	0.9485	pathogenic	-0.273	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/D	0.3413	ambiguous	0.2848	benign	-1.087	Destabilizing	0.997	D	0.748	deleterious	N	0.476049138	None	None	N
E/F	0.9201	likely_pathogenic	0.9134	pathogenic	0.413	Stabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
E/G	0.6692	likely_pathogenic	0.6629	pathogenic	-0.927	Destabilizing	0.999	D	0.695	prob.delet.	N	0.504410516	None	None	N
E/H	0.8528	likely_pathogenic	0.8382	pathogenic	0.213	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/I	0.6594	likely_pathogenic	0.6369	pathogenic	0.707	Stabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
E/K	0.5507	ambiguous	0.5676	pathogenic	-0.42	Destabilizing	0.997	D	0.805	deleterious	N	0.492040253	None	None	N
E/L	0.7911	likely_pathogenic	0.7791	pathogenic	0.707	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/M	0.7486	likely_pathogenic	0.7299	pathogenic	1.091	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/N	0.7051	likely_pathogenic	0.6639	pathogenic	-1.102	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
E/P	0.9739	likely_pathogenic	0.9784	pathogenic	0.329	Stabilizing	0.999	D	0.739	deleterious	None	None	None	None	N
E/Q	0.3635	ambiguous	0.3498	ambiguous	-0.882	Destabilizing	0.999	D	0.779	deleterious	N	0.482836768	None	None	N
E/R	0.729	likely_pathogenic	0.7501	pathogenic	-0.087	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
E/S	0.5885	likely_pathogenic	0.5528	ambiguous	-1.457	Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
E/T	0.6029	likely_pathogenic	0.5714	pathogenic	-1.079	Destabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	N
E/V	0.4985	ambiguous	0.477	ambiguous	0.329	Stabilizing	0.999	D	0.731	deleterious	N	0.490243054	None	None	N
E/W	0.9781	likely_pathogenic	0.9788	pathogenic	0.682	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Y	0.8975	likely_pathogenic	0.8872	pathogenic	0.703	Stabilizing	1.0	D	0.846	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.