TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24053	72382;72383;72384	chr2:178573975;178573974;178573973	chr2:179438702;179438701;179438700
N2AB	22412	67459;67460;67461	chr2:178573975;178573974;178573973	chr2:179438702;179438701;179438700
N2A	21485	64678;64679;64680	chr2:178573975;178573974;178573973	chr2:179438702;179438701;179438700
N2B	14988	45187;45188;45189	chr2:178573975;178573974;178573973	chr2:179438702;179438701;179438700
Novex-1	15113	45562;45563;45564	chr2:178573975;178573974;178573973	chr2:179438702;179438701;179438700
Novex-2	15180	45763;45764;45765	chr2:178573975;178573974;178573973	chr2:179438702;179438701;179438700
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-131
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.2868
• 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/D	None	None	1.0	D	0.844	0.875	0.922313786736	gnomAD-4.0.0	1.59221E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85948E-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	0.7271	likely_pathogenic	0.7015	pathogenic	-1.813	Destabilizing	0.999	D	0.603	neutral	N	0.505940019	None	None	I
V/C	0.9214	likely_pathogenic	0.9089	pathogenic	-1.382	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
V/D	0.9924	likely_pathogenic	0.9893	pathogenic	-1.683	Destabilizing	1.0	D	0.844	deleterious	D	0.621054299	None	None	I
V/E	0.9857	likely_pathogenic	0.98	pathogenic	-1.635	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
V/F	0.6275	likely_pathogenic	0.5904	pathogenic	-1.337	Destabilizing	1.0	D	0.815	deleterious	D	0.543864912	None	None	I
V/G	0.879	likely_pathogenic	0.847	pathogenic	-2.198	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.589015577	None	None	I
V/H	0.9905	likely_pathogenic	0.9872	pathogenic	-1.699	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
V/I	0.0928	likely_benign	0.0961	benign	-0.824	Destabilizing	0.997	D	0.547	neutral	N	0.478731988	None	None	I
V/K	0.9858	likely_pathogenic	0.9797	pathogenic	-1.427	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
V/L	0.6159	likely_pathogenic	0.5779	pathogenic	-0.824	Destabilizing	0.997	D	0.627	neutral	D	0.552142476	None	None	I
V/M	0.6054	likely_pathogenic	0.5562	ambiguous	-0.69	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
V/N	0.9759	likely_pathogenic	0.9682	pathogenic	-1.299	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
V/P	0.9906	likely_pathogenic	0.9866	pathogenic	-1.12	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
V/Q	0.9817	likely_pathogenic	0.975	pathogenic	-1.422	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
V/R	0.9717	likely_pathogenic	0.9617	pathogenic	-0.962	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
V/S	0.908	likely_pathogenic	0.8844	pathogenic	-1.921	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
V/T	0.7921	likely_pathogenic	0.7499	pathogenic	-1.75	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
V/W	0.9917	likely_pathogenic	0.9892	pathogenic	-1.552	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
V/Y	0.9502	likely_pathogenic	0.9329	pathogenic	-1.262	Destabilizing	1.0	D	0.813	deleterious	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.