TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7395	22408;22409;22410	chr2:178722716;178722715;178722714	chr2:179587443;179587442;179587441
N2AB	7078	21457;21458;21459	chr2:178722716;178722715;178722714	chr2:179587443;179587442;179587441
N2A	6151	18676;18677;18678	chr2:178722716;178722715;178722714	chr2:179587443;179587442;179587441
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-58
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0792
• Site annotation: disulfide
• 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
C/R	None	None	1.0	D	0.845	0.689	0.860195380671	gnomAD-4.0.0	2.40064E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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
C/A	0.8956	likely_pathogenic	0.9435	pathogenic	-1.595	Destabilizing	0.993	D	0.655	neutral	None	None	disulfide	None	N
C/D	0.9996	likely_pathogenic	0.9999	pathogenic	-1.182	Destabilizing	1.0	D	0.839	deleterious	None	None	disulfide	None	N
C/E	0.9996	likely_pathogenic	0.9999	pathogenic	-0.937	Destabilizing	1.0	D	0.841	deleterious	None	None	disulfide	None	N
C/F	0.8334	likely_pathogenic	0.9283	pathogenic	-1.0	Destabilizing	0.599	D	0.665	neutral	D	0.55972551	disulfide	None	N
C/G	0.8345	likely_pathogenic	0.9378	pathogenic	-1.958	Destabilizing	0.995	D	0.813	deleterious	D	0.561246447	disulfide	None	N
C/H	0.9978	likely_pathogenic	0.9994	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	disulfide	None	N
C/I	0.8416	likely_pathogenic	0.9294	pathogenic	-0.609	Destabilizing	1.0	D	0.761	deleterious	None	None	disulfide	None	N
C/K	0.9997	likely_pathogenic	0.9999	pathogenic	-0.74	Destabilizing	1.0	D	0.839	deleterious	None	None	disulfide	None	N
C/L	0.7546	likely_pathogenic	0.8705	pathogenic	-0.609	Destabilizing	0.997	D	0.723	prob.delet.	None	None	disulfide	None	N
C/M	0.9406	likely_pathogenic	0.9724	pathogenic	-0.022	Destabilizing	1.0	D	0.795	deleterious	None	None	disulfide	None	N
C/N	0.9973	likely_pathogenic	0.9993	pathogenic	-1.347	Destabilizing	1.0	D	0.842	deleterious	None	None	disulfide	None	N
C/P	0.999	likely_pathogenic	0.9997	pathogenic	-0.916	Destabilizing	1.0	D	0.847	deleterious	None	None	disulfide	None	N
C/Q	0.9984	likely_pathogenic	0.9995	pathogenic	-0.865	Destabilizing	1.0	D	0.857	deleterious	None	None	disulfide	None	N
C/R	0.9943	likely_pathogenic	0.9982	pathogenic	-1.252	Destabilizing	1.0	D	0.845	deleterious	D	0.561246447	disulfide	None	N
C/S	0.9589	likely_pathogenic	0.9854	pathogenic	-1.669	Destabilizing	1.0	D	0.765	deleterious	D	0.561246447	disulfide	None	N
C/T	0.9747	likely_pathogenic	0.99	pathogenic	-1.23	Destabilizing	1.0	D	0.765	deleterious	None	None	disulfide	None	N
C/V	0.7177	likely_pathogenic	0.8382	pathogenic	-0.916	Destabilizing	0.998	D	0.726	prob.delet.	None	None	disulfide	None	N
C/W	0.988	likely_pathogenic	0.9965	pathogenic	-1.34	Destabilizing	0.991	D	0.675	prob.neutral	D	0.561246447	disulfide	None	N
C/Y	0.9714	likely_pathogenic	0.9921	pathogenic	-1.129	Destabilizing	1.0	D	0.788	deleterious	D	0.561246447	disulfide	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.