TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20090	60493;60494;60495	chr2:178591457;178591456;178591455	chr2:179456184;179456183;179456182
N2AB	18449	55570;55571;55572	chr2:178591457;178591456;178591455	chr2:179456184;179456183;179456182
N2A	17522	52789;52790;52791	chr2:178591457;178591456;178591455	chr2:179456184;179456183;179456182
N2B	11025	33298;33299;33300	chr2:178591457;178591456;178591455	chr2:179456184;179456183;179456182
Novex-1	11150	33673;33674;33675	chr2:178591457;178591456;178591455	chr2:179456184;179456183;179456182
Novex-2	11217	33874;33875;33876	chr2:178591457;178591456;178591455	chr2:179456184;179456183;179456182
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-120
• Domain position: 11
• Structural Position: 16
• Q(SASA): 0.1739
• 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/E	None	None	1.0	D	0.671	0.764	0.893265043611	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.6279	likely_pathogenic	0.5307	ambiguous	-1.785	Destabilizing	0.999	D	0.469	neutral	N	0.516554083	None	None	N
V/C	0.905	likely_pathogenic	0.8787	pathogenic	-1.282	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
V/D	0.9889	likely_pathogenic	0.9846	pathogenic	-1.824	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
V/E	0.947	likely_pathogenic	0.9275	pathogenic	-1.735	Destabilizing	1.0	D	0.671	neutral	D	0.5559188	None	None	N
V/F	0.6546	likely_pathogenic	0.5795	pathogenic	-1.185	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/G	0.8034	likely_pathogenic	0.7783	pathogenic	-2.205	Highly Destabilizing	1.0	D	0.693	prob.neutral	N	0.516329702	None	None	N
V/H	0.9845	likely_pathogenic	0.9741	pathogenic	-1.821	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
V/I	0.1294	likely_benign	0.1133	benign	-0.685	Destabilizing	0.997	D	0.476	neutral	D	0.524885565	None	None	N
V/K	0.9518	likely_pathogenic	0.9278	pathogenic	-1.6	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
V/L	0.5774	likely_pathogenic	0.4902	ambiguous	-0.685	Destabilizing	0.997	D	0.493	neutral	N	0.510743387	None	None	N
V/M	0.5127	ambiguous	0.4196	ambiguous	-0.561	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
V/N	0.9686	likely_pathogenic	0.955	pathogenic	-1.561	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
V/P	0.9939	likely_pathogenic	0.9909	pathogenic	-1.019	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
V/Q	0.9187	likely_pathogenic	0.8926	pathogenic	-1.598	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
V/R	0.935	likely_pathogenic	0.9153	pathogenic	-1.186	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
V/S	0.8609	likely_pathogenic	0.8131	pathogenic	-2.154	Highly Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
V/T	0.6997	likely_pathogenic	0.6107	pathogenic	-1.943	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
V/W	0.9927	likely_pathogenic	0.989	pathogenic	-1.526	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
V/Y	0.9587	likely_pathogenic	0.9393	pathogenic	-1.196	Destabilizing	1.0	D	0.703	prob.neutral	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.