TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7742	23449;23450;23451	chr2:178720538;178720537;178720536	chr2:179585265;179585264;179585263
N2AB	7425	22498;22499;22500	chr2:178720538;178720537;178720536	chr2:179585265;179585264;179585263
N2A	6498	19717;19718;19719	chr2:178720538;178720537;178720536	chr2:179585265;179585264;179585263
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-62
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1373
• 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
V/A	rs1553907288	None	0.454	N	0.571	0.256	0.519460762563	gnomAD-4.0.0	2.05294E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69873E-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
V/A	0.7016	likely_pathogenic	0.7872	pathogenic	-1.864	Destabilizing	0.454	N	0.571	neutral	N	0.514089781	None	None	N
V/C	0.9388	likely_pathogenic	0.9522	pathogenic	-1.276	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
V/D	0.9822	likely_pathogenic	0.9912	pathogenic	-2.575	Highly Destabilizing	0.934	D	0.747	deleterious	D	0.524288132	None	None	N
V/E	0.9435	likely_pathogenic	0.9681	pathogenic	-2.338	Highly Destabilizing	0.949	D	0.707	prob.neutral	None	None	None	None	N
V/F	0.4418	ambiguous	0.5419	ambiguous	-1.175	Destabilizing	0.934	D	0.709	prob.delet.	N	0.493791867	None	None	N
V/G	0.7995	likely_pathogenic	0.865	pathogenic	-2.382	Highly Destabilizing	0.801	D	0.697	prob.neutral	D	0.530040669	None	None	N
V/H	0.9774	likely_pathogenic	0.9869	pathogenic	-2.109	Highly Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
V/I	0.0733	likely_benign	0.0782	benign	-0.413	Destabilizing	0.005	N	0.152	neutral	N	0.359338941	None	None	N
V/K	0.9639	likely_pathogenic	0.9781	pathogenic	-1.624	Destabilizing	0.949	D	0.708	prob.delet.	None	None	None	None	N
V/L	0.1917	likely_benign	0.2594	benign	-0.413	Destabilizing	0.267	N	0.431	neutral	N	0.348329726	None	None	N
V/M	0.2939	likely_benign	0.3842	ambiguous	-0.398	Destabilizing	0.949	D	0.652	neutral	None	None	None	None	N
V/N	0.9455	likely_pathogenic	0.9718	pathogenic	-2.009	Highly Destabilizing	0.949	D	0.777	deleterious	None	None	None	None	N
V/P	0.9557	likely_pathogenic	0.9728	pathogenic	-0.872	Destabilizing	0.974	D	0.745	deleterious	None	None	None	None	N
V/Q	0.9319	likely_pathogenic	0.96	pathogenic	-1.833	Destabilizing	0.974	D	0.725	prob.delet.	None	None	None	None	N
V/R	0.9521	likely_pathogenic	0.9704	pathogenic	-1.525	Destabilizing	0.974	D	0.793	deleterious	None	None	None	None	N
V/S	0.9005	likely_pathogenic	0.9429	pathogenic	-2.565	Highly Destabilizing	0.172	N	0.513	neutral	None	None	None	None	N
V/T	0.8117	likely_pathogenic	0.8761	pathogenic	-2.179	Highly Destabilizing	0.728	D	0.58	neutral	None	None	None	None	N
V/W	0.9657	likely_pathogenic	0.9774	pathogenic	-1.679	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
V/Y	0.8996	likely_pathogenic	0.9317	pathogenic	-1.238	Destabilizing	0.991	D	0.731	prob.delet.	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.