TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	993	3202;3203;3204	chr2:178782929;178782928;178782927	chr2:179647656;179647655;179647654
N2AB	993	3202;3203;3204	chr2:178782929;178782928;178782927	chr2:179647656;179647655;179647654
N2A	993	3202;3203;3204	chr2:178782929;178782928;178782927	chr2:179647656;179647655;179647654
N2B	947	3064;3065;3066	chr2:178782929;178782928;178782927	chr2:179647656;179647655;179647654
Novex-1	947	3064;3065;3066	chr2:178782929;178782928;178782927	chr2:179647656;179647655;179647654
Novex-2	947	3064;3065;3066	chr2:178782929;178782928;178782927	chr2:179647656;179647655;179647654
Novex-3	993	3202;3203;3204	chr2:178782929;178782928;178782927	chr2:179647656;179647655;179647654

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-3
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.397
• 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
F/L	rs371838857	-0.907	0.91	N	0.611	0.422	0.455173453901	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	1.23031E-04	0	None	0	0	None	0	None	0	0	0
F/L	rs371838857	-0.907	0.91	N	0.611	0.422	0.455173453901	gnomAD-4.0.0	2.05223E-06	None	None	None	None	N	None	8.96164E-05	0	None	0	0	None	0	0	0	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
F/A	0.9709	likely_pathogenic	0.9874	pathogenic	-2.08	Highly Destabilizing	0.985	D	0.673	neutral	None	None	None	None	N
F/C	0.8986	likely_pathogenic	0.9467	pathogenic	-1.122	Destabilizing	1.0	D	0.713	prob.delet.	N	0.480281456	None	None	N
F/D	0.9906	likely_pathogenic	0.9959	pathogenic	-0.497	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
F/E	0.9898	likely_pathogenic	0.9958	pathogenic	-0.414	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
F/G	0.9869	likely_pathogenic	0.994	pathogenic	-2.41	Highly Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
F/H	0.8934	likely_pathogenic	0.9294	pathogenic	-0.773	Destabilizing	0.991	D	0.63	neutral	None	None	None	None	N
F/I	0.8318	likely_pathogenic	0.9154	pathogenic	-1.102	Destabilizing	0.98	D	0.618	neutral	N	0.471645818	None	None	N
F/K	0.9902	likely_pathogenic	0.9954	pathogenic	-1.01	Destabilizing	0.996	D	0.708	prob.delet.	None	None	None	None	N
F/L	0.9816	likely_pathogenic	0.9898	pathogenic	-1.102	Destabilizing	0.91	D	0.611	neutral	N	0.439807788	None	None	N
F/M	0.9224	likely_pathogenic	0.9532	pathogenic	-0.887	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
F/N	0.9657	likely_pathogenic	0.9818	pathogenic	-0.988	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
F/P	0.999	likely_pathogenic	0.9995	pathogenic	-1.42	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
F/Q	0.9755	likely_pathogenic	0.9876	pathogenic	-1.063	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
F/R	0.9718	likely_pathogenic	0.9864	pathogenic	-0.423	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
F/S	0.9161	likely_pathogenic	0.9622	pathogenic	-1.852	Destabilizing	0.994	D	0.649	neutral	N	0.45889649	None	None	N
F/T	0.9555	likely_pathogenic	0.9807	pathogenic	-1.677	Destabilizing	0.996	D	0.66	neutral	None	None	None	None	N
F/V	0.8046	likely_pathogenic	0.9019	pathogenic	-1.42	Destabilizing	0.961	D	0.635	neutral	N	0.428963225	None	None	N
F/W	0.7797	likely_pathogenic	0.8326	pathogenic	-0.289	Destabilizing	0.996	D	0.626	neutral	None	None	None	None	N
F/Y	0.3094	likely_benign	0.3353	benign	-0.463	Destabilizing	0.122	N	0.267	neutral	N	0.40884307	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.