TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32042	96349;96350;96351	chr2:178544020;178544019;178544018	chr2:179408747;179408746;179408745
N2AB	30401	91426;91427;91428	chr2:178544020;178544019;178544018	chr2:179408747;179408746;179408745
N2A	29474	88645;88646;88647	chr2:178544020;178544019;178544018	chr2:179408747;179408746;179408745
N2B	22977	69154;69155;69156	chr2:178544020;178544019;178544018	chr2:179408747;179408746;179408745
Novex-1	23102	69529;69530;69531	chr2:178544020;178544019;178544018	chr2:179408747;179408746;179408745
Novex-2	23169	69730;69731;69732	chr2:178544020;178544019;178544018	chr2:179408747;179408746;179408745
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-153
• Domain position: 26
• Structural Position: 42
• Q(SASA): 0.354
• 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
P/L	rs879110168	None	0.946	D	0.712	0.676	None	gnomAD-4.0.0	2.73713E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69857E-06	0	1.65678E-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
P/A	0.8877	likely_pathogenic	0.8332	pathogenic	-0.646	Destabilizing	0.716	D	0.536	neutral	D	0.575610126	None	None	N
P/C	0.9859	likely_pathogenic	0.9777	pathogenic	-0.538	Destabilizing	0.994	D	0.765	deleterious	None	None	None	None	N
P/D	0.9736	likely_pathogenic	0.9631	pathogenic	-0.611	Destabilizing	0.959	D	0.697	prob.neutral	None	None	None	None	N
P/E	0.9677	likely_pathogenic	0.949	pathogenic	-0.733	Destabilizing	0.921	D	0.705	prob.neutral	None	None	None	None	N
P/F	0.9855	likely_pathogenic	0.9768	pathogenic	-0.89	Destabilizing	0.994	D	0.775	deleterious	None	None	None	None	N
P/G	0.9717	likely_pathogenic	0.9617	pathogenic	-0.786	Destabilizing	0.769	D	0.656	neutral	None	None	None	None	N
P/H	0.941	likely_pathogenic	0.913	pathogenic	-0.409	Destabilizing	0.994	D	0.729	prob.delet.	None	None	None	None	N
P/I	0.9019	likely_pathogenic	0.8535	pathogenic	-0.424	Destabilizing	0.959	D	0.737	prob.delet.	None	None	None	None	N
P/K	0.9591	likely_pathogenic	0.9437	pathogenic	-0.603	Destabilizing	0.921	D	0.703	prob.neutral	None	None	None	None	N
P/L	0.8182	likely_pathogenic	0.7311	pathogenic	-0.424	Destabilizing	0.946	D	0.712	prob.delet.	D	0.640799013	None	None	N
P/M	0.9421	likely_pathogenic	0.9098	pathogenic	-0.353	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
P/N	0.9587	likely_pathogenic	0.9458	pathogenic	-0.244	Destabilizing	0.921	D	0.675	neutral	None	None	None	None	N
P/Q	0.9381	likely_pathogenic	0.9085	pathogenic	-0.533	Destabilizing	0.946	D	0.706	prob.neutral	D	0.575610126	None	None	N
P/R	0.938	likely_pathogenic	0.9142	pathogenic	-0.023	Destabilizing	0.946	D	0.706	prob.neutral	D	0.649914155	None	None	N
P/S	0.9471	likely_pathogenic	0.9152	pathogenic	-0.561	Destabilizing	0.035	N	0.353	neutral	D	0.581851096	None	None	N
P/T	0.8849	likely_pathogenic	0.8276	pathogenic	-0.591	Destabilizing	0.898	D	0.708	prob.delet.	D	0.633894794	None	None	N
P/V	0.8788	likely_pathogenic	0.8276	pathogenic	-0.463	Destabilizing	0.959	D	0.676	prob.neutral	None	None	None	None	N
P/W	0.9951	likely_pathogenic	0.9919	pathogenic	-0.967	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
P/Y	0.9793	likely_pathogenic	0.9691	pathogenic	-0.683	Destabilizing	0.998	D	0.774	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.