TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31404	94435;94436;94437	chr2:178547416;178547415;178547414	chr2:179412143;179412142;179412141
N2AB	29763	89512;89513;89514	chr2:178547416;178547415;178547414	chr2:179412143;179412142;179412141
N2A	28836	86731;86732;86733	chr2:178547416;178547415;178547414	chr2:179412143;179412142;179412141
N2B	22339	67240;67241;67242	chr2:178547416;178547415;178547414	chr2:179412143;179412142;179412141
Novex-1	22464	67615;67616;67617	chr2:178547416;178547415;178547414	chr2:179412143;179412142;179412141
Novex-2	22531	67816;67817;67818	chr2:178547416;178547415;178547414	chr2:179412143;179412142;179412141
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-116
• Domain position: 97
• Structural Position: 132
• Q(SASA): 0.9904
• 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
H/N	rs1409641656	0.215	0.997	N	0.622	0.329	0.271763555656	gnomAD-4.0.0	1.63067E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.46619E-05	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
H/A	0.928	likely_pathogenic	0.9136	pathogenic	0.546	Stabilizing	0.998	D	0.457	neutral	None	None	None	None	I
H/C	0.7233	likely_pathogenic	0.6944	pathogenic	0.811	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
H/D	0.7176	likely_pathogenic	0.727	pathogenic	0.059	Stabilizing	0.999	D	0.663	prob.neutral	N	0.451136302	None	None	I
H/E	0.9399	likely_pathogenic	0.9309	pathogenic	0.064	Stabilizing	0.998	D	0.636	neutral	None	None	None	None	I
H/F	0.6472	likely_pathogenic	0.6425	pathogenic	1.044	Stabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	I
H/G	0.9551	likely_pathogenic	0.9333	pathogenic	0.305	Stabilizing	0.998	D	0.454	neutral	None	None	None	None	I
H/I	0.9041	likely_pathogenic	0.8857	pathogenic	1.139	Stabilizing	0.999	D	0.706	prob.delet.	None	None	None	None	I
H/K	0.9675	likely_pathogenic	0.9566	pathogenic	0.509	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	I
H/L	0.47	ambiguous	0.4251	ambiguous	1.139	Stabilizing	0.999	D	0.649	prob.neutral	N	0.477936114	None	None	I
H/M	0.891	likely_pathogenic	0.8824	pathogenic	0.845	Stabilizing	1.0	D	0.689	prob.delet.	None	None	None	None	I
H/N	0.397	ambiguous	0.3885	ambiguous	0.487	Stabilizing	0.997	D	0.622	neutral	N	0.469356703	None	None	I
H/P	0.6054	likely_pathogenic	0.5317	ambiguous	0.967	Stabilizing	0.999	D	0.651	prob.neutral	N	0.461664185	None	None	I
H/Q	0.9149	likely_pathogenic	0.9026	pathogenic	0.543	Stabilizing	0.999	D	0.706	prob.delet.	N	0.505720148	None	None	I
H/R	0.9445	likely_pathogenic	0.923	pathogenic	-0.017	Destabilizing	0.999	D	0.697	prob.delet.	N	0.461664185	None	None	I
H/S	0.7893	likely_pathogenic	0.768	pathogenic	0.59	Stabilizing	0.999	D	0.629	neutral	None	None	None	None	I
H/T	0.9299	likely_pathogenic	0.9143	pathogenic	0.691	Stabilizing	0.999	D	0.663	prob.neutral	None	None	None	None	I
H/V	0.9166	likely_pathogenic	0.8992	pathogenic	0.967	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
H/W	0.7843	likely_pathogenic	0.7527	pathogenic	0.945	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
H/Y	0.2465	likely_benign	0.228	benign	1.262	Stabilizing	0.997	D	0.549	neutral	N	0.462180015	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.