TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3869	11830;11831;11832	chr2:178741628;178741627;178741626	chr2:179606355;179606354;179606353
N2AB	3552	10879;10880;10881	chr2:178741628;178741627;178741626	chr2:179606355;179606354;179606353
N2A	None	None	chr2:None	chr2:None
N2B	3506	10741;10742;10743	chr2:178741628;178741627;178741626	chr2:179606355;179606354;179606353
Novex-1	3631	11116;11117;11118	chr2:178741628;178741627;178741626	chr2:179606355;179606354;179606353
Novex-2	3698	11317;11318;11319	chr2:178741628;178741627;178741626	chr2:179606355;179606354;179606353
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-27
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.5136
• 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/L	rs747929496	-0.079	0.9	N	0.324	0.199	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
V/L	rs747929496	-0.079	0.9	N	0.324	0.199	None	gnomAD-4.0.0	7.52617E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99457E-06	0	1.65667E-05

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	0.4007	ambiguous	0.3414	ambiguous	-0.657	Destabilizing	0.948	D	0.457	neutral	N	0.501358566	None	None	I
V/C	0.8236	likely_pathogenic	0.8215	pathogenic	-0.654	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
V/D	0.6423	likely_pathogenic	0.5993	pathogenic	-0.327	Destabilizing	0.999	D	0.748	deleterious	N	0.505100264	None	None	I
V/E	0.5871	likely_pathogenic	0.5391	ambiguous	-0.415	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	I
V/F	0.2887	likely_benign	0.249	benign	-0.684	Destabilizing	0.994	D	0.688	prob.neutral	N	0.510971288	None	None	I
V/G	0.4959	ambiguous	0.4364	ambiguous	-0.84	Destabilizing	0.999	D	0.742	deleterious	D	0.570702888	None	None	I
V/H	0.7511	likely_pathogenic	0.7167	pathogenic	-0.337	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
V/I	0.0967	likely_benign	0.0896	benign	-0.311	Destabilizing	0.198	N	0.19	neutral	N	0.502297159	None	None	I
V/K	0.6463	likely_pathogenic	0.5915	pathogenic	-0.594	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
V/L	0.2946	likely_benign	0.2514	benign	-0.311	Destabilizing	0.9	D	0.324	neutral	N	0.482808783	None	None	I
V/M	0.3122	likely_benign	0.2596	benign	-0.359	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	I
V/N	0.5575	ambiguous	0.4905	ambiguous	-0.325	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
V/P	0.9386	likely_pathogenic	0.9122	pathogenic	-0.39	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
V/Q	0.6056	likely_pathogenic	0.5557	ambiguous	-0.546	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
V/R	0.5042	ambiguous	0.4772	ambiguous	-0.062	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	I
V/S	0.4075	ambiguous	0.3531	ambiguous	-0.744	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
V/T	0.406	ambiguous	0.3541	ambiguous	-0.726	Destabilizing	0.992	D	0.489	neutral	None	None	None	None	I
V/W	0.9231	likely_pathogenic	0.9129	pathogenic	-0.775	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
V/Y	0.7163	likely_pathogenic	0.6958	pathogenic	-0.488	Destabilizing	0.999	D	0.677	prob.neutral	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.