TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7900	23923;23924;23925	chr2:178719794;178719793;178719792	chr2:179584521;179584520;179584519
N2AB	7583	22972;22973;22974	chr2:178719794;178719793;178719792	chr2:179584521;179584520;179584519
N2A	6656	20191;20192;20193	chr2:178719794;178719793;178719792	chr2:179584521;179584520;179584519
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-64
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1681
• 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
V/A	None	None	0.645	N	0.463	0.499	0.67724314777	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.4655	ambiguous	0.4635	ambiguous	-1.77	Destabilizing	0.645	D	0.463	neutral	N	0.503195289	None	None	I
V/C	0.9345	likely_pathogenic	0.9249	pathogenic	-1.704	Destabilizing	0.995	D	0.655	neutral	None	None	None	None	I
V/D	0.9568	likely_pathogenic	0.9371	pathogenic	-1.7	Destabilizing	0.928	D	0.765	deleterious	D	0.575922386	None	None	I
V/E	0.8717	likely_pathogenic	0.8538	pathogenic	-1.655	Destabilizing	0.945	D	0.735	prob.delet.	None	None	None	None	I
V/F	0.5335	ambiguous	0.4798	ambiguous	-1.49	Destabilizing	0.864	D	0.729	prob.delet.	D	0.535661725	None	None	I
V/G	0.7098	likely_pathogenic	0.6669	pathogenic	-2.127	Highly Destabilizing	0.928	D	0.753	deleterious	D	0.534598541	None	None	I
V/H	0.9686	likely_pathogenic	0.9615	pathogenic	-1.632	Destabilizing	0.995	D	0.701	prob.neutral	None	None	None	None	I
V/I	0.1085	likely_benign	0.096	benign	-0.861	Destabilizing	0.006	N	0.244	neutral	N	0.493586957	None	None	I
V/K	0.9171	likely_pathogenic	0.9141	pathogenic	-1.308	Destabilizing	0.945	D	0.734	prob.delet.	None	None	None	None	I
V/L	0.505	ambiguous	0.4682	ambiguous	-0.861	Destabilizing	0.114	N	0.401	neutral	D	0.528024722	None	None	I
V/M	0.349	ambiguous	0.3282	benign	-0.894	Destabilizing	0.894	D	0.719	prob.delet.	None	None	None	None	I
V/N	0.9017	likely_pathogenic	0.8624	pathogenic	-1.273	Destabilizing	0.981	D	0.754	deleterious	None	None	None	None	I
V/P	0.9798	likely_pathogenic	0.9708	pathogenic	-1.131	Destabilizing	0.981	D	0.749	deleterious	None	None	None	None	I
V/Q	0.8826	likely_pathogenic	0.8653	pathogenic	-1.419	Destabilizing	0.981	D	0.728	prob.delet.	None	None	None	None	I
V/R	0.8828	likely_pathogenic	0.8695	pathogenic	-0.875	Destabilizing	0.945	D	0.755	deleterious	None	None	None	None	I
V/S	0.7181	likely_pathogenic	0.6783	pathogenic	-1.908	Destabilizing	0.945	D	0.745	deleterious	None	None	None	None	I
V/T	0.5063	ambiguous	0.5177	ambiguous	-1.737	Destabilizing	0.707	D	0.678	prob.neutral	None	None	None	None	I
V/W	0.9879	likely_pathogenic	0.9842	pathogenic	-1.66	Destabilizing	0.995	D	0.669	neutral	None	None	None	None	I
V/Y	0.9376	likely_pathogenic	0.9213	pathogenic	-1.335	Destabilizing	0.945	D	0.724	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.