TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7355	22288;22289;22290	chr2:178722836;178722835;178722834	chr2:179587563;179587562;179587561
N2AB	7038	21337;21338;21339	chr2:178722836;178722835;178722834	chr2:179587563;179587562;179587561
N2A	6111	18556;18557;18558	chr2:178722836;178722835;178722834	chr2:179587563;179587562;179587561
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-58
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.1861
• 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
S/P	None	None	0.979	D	0.702	0.606	0.519187973786	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
S/A	0.0896	likely_benign	0.1034	benign	-0.719	Destabilizing	0.472	N	0.592	neutral	N	0.518362237	None	None	N
S/C	0.1441	likely_benign	0.1836	benign	-0.388	Destabilizing	0.994	D	0.659	neutral	N	0.517402431	None	None	N
S/D	0.5977	likely_pathogenic	0.7316	pathogenic	-0.641	Destabilizing	0.854	D	0.663	neutral	None	None	None	None	N
S/E	0.683	likely_pathogenic	0.7867	pathogenic	-0.538	Destabilizing	0.742	D	0.646	neutral	None	None	None	None	N
S/F	0.1338	likely_benign	0.1577	benign	-0.531	Destabilizing	0.015	N	0.537	neutral	N	0.497234261	None	None	N
S/G	0.1794	likely_benign	0.2131	benign	-1.077	Destabilizing	0.854	D	0.63	neutral	None	None	None	None	N
S/H	0.3886	ambiguous	0.4579	ambiguous	-1.434	Destabilizing	0.91	D	0.682	prob.neutral	None	None	None	None	N
S/I	0.1752	likely_benign	0.2302	benign	0.16	Stabilizing	0.835	D	0.694	prob.neutral	None	None	None	None	N
S/K	0.8013	likely_pathogenic	0.8948	pathogenic	-0.58	Destabilizing	0.037	N	0.488	neutral	None	None	None	None	N
S/L	0.1069	likely_benign	0.1283	benign	0.16	Stabilizing	0.59	D	0.647	neutral	None	None	None	None	N
S/M	0.2158	likely_benign	0.2337	benign	0.245	Stabilizing	0.953	D	0.675	prob.neutral	None	None	None	None	N
S/N	0.2216	likely_benign	0.2613	benign	-0.842	Destabilizing	0.854	D	0.655	neutral	None	None	None	None	N
S/P	0.9251	likely_pathogenic	0.9736	pathogenic	-0.097	Destabilizing	0.979	D	0.702	prob.neutral	D	0.534835123	None	None	N
S/Q	0.5865	likely_pathogenic	0.673	pathogenic	-0.753	Destabilizing	0.91	D	0.677	prob.neutral	None	None	None	None	N
S/R	0.7048	likely_pathogenic	0.8324	pathogenic	-0.718	Destabilizing	0.835	D	0.713	prob.delet.	None	None	None	None	N
S/T	0.0941	likely_benign	0.1008	benign	-0.695	Destabilizing	0.028	N	0.467	neutral	N	0.443960479	None	None	N
S/V	0.1842	likely_benign	0.2274	benign	-0.097	Destabilizing	0.742	D	0.67	neutral	None	None	None	None	N
S/W	0.2929	likely_benign	0.36	ambiguous	-0.662	Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	N
S/Y	0.152	likely_benign	0.1957	benign	-0.321	Destabilizing	0.063	N	0.539	neutral	N	0.494271747	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.