TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2205	6838;6839;6840	chr2:178775098;178775097;178775096	chr2:179639825;179639824;179639823
N2AB	2205	6838;6839;6840	chr2:178775098;178775097;178775096	chr2:179639825;179639824;179639823
N2A	2205	6838;6839;6840	chr2:178775098;178775097;178775096	chr2:179639825;179639824;179639823
N2B	2159	6700;6701;6702	chr2:178775098;178775097;178775096	chr2:179639825;179639824;179639823
Novex-1	2159	6700;6701;6702	chr2:178775098;178775097;178775096	chr2:179639825;179639824;179639823
Novex-2	2159	6700;6701;6702	chr2:178775098;178775097;178775096	chr2:179639825;179639824;179639823
Novex-3	2205	6838;6839;6840	chr2:178775098;178775097;178775096	chr2:179639825;179639824;179639823

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-11
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.3745
• 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/M	rs2154345518	None	1.0	D	0.749	0.722	0.760968267486	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.9253E-04	None	0	0	0	0	0
V/M	rs2154345518	None	1.0	D	0.749	0.722	0.760968267486	gnomAD-4.0.0	6.56556E-06	None	None	None	None	N	None	0	0	None	0	1.92976E-04	None	0	0	0	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	0.676	likely_pathogenic	0.6881	pathogenic	-1.862	Destabilizing	0.999	D	0.664	neutral	D	0.610517078	None	None	N
V/C	0.9453	likely_pathogenic	0.9421	pathogenic	-0.98	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/D	0.993	likely_pathogenic	0.9941	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/E	0.9809	likely_pathogenic	0.984	pathogenic	-2.299	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.759446366	None	None	N
V/F	0.8297	likely_pathogenic	0.8476	pathogenic	-1.282	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/G	0.7926	likely_pathogenic	0.8113	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.609787616	None	None	N
V/H	0.9948	likely_pathogenic	0.9955	pathogenic	-1.941	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.1535	likely_benign	0.1543	benign	-0.758	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
V/K	0.9865	likely_pathogenic	0.9884	pathogenic	-1.676	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/L	0.7134	likely_pathogenic	0.7086	pathogenic	-0.758	Destabilizing	0.997	D	0.685	prob.neutral	D	0.65591182	None	None	N
V/M	0.6315	likely_pathogenic	0.6435	pathogenic	-0.451	Destabilizing	1.0	D	0.749	deleterious	D	0.700459701	None	None	N
V/N	0.973	likely_pathogenic	0.9753	pathogenic	-1.719	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/P	0.9461	likely_pathogenic	0.9534	pathogenic	-1.099	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/Q	0.9805	likely_pathogenic	0.9829	pathogenic	-1.746	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/R	0.9805	likely_pathogenic	0.983	pathogenic	-1.25	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/S	0.9044	likely_pathogenic	0.9128	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/T	0.7483	likely_pathogenic	0.759	pathogenic	-1.951	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
V/W	0.9961	likely_pathogenic	0.9967	pathogenic	-1.737	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Y	0.9829	likely_pathogenic	0.9853	pathogenic	-1.363	Destabilizing	1.0	D	0.787	deleterious	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.