TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18875	56848;56849;56850	chr2:178599170;178599169;178599168	chr2:179463897;179463896;179463895
N2AB	17234	51925;51926;51927	chr2:178599170;178599169;178599168	chr2:179463897;179463896;179463895
N2A	16307	49144;49145;49146	chr2:178599170;178599169;178599168	chr2:179463897;179463896;179463895
N2B	9810	29653;29654;29655	chr2:178599170;178599169;178599168	chr2:179463897;179463896;179463895
Novex-1	9935	30028;30029;30030	chr2:178599170;178599169;178599168	chr2:179463897;179463896;179463895
Novex-2	10002	30229;30230;30231	chr2:178599170;178599169;178599168	chr2:179463897;179463896;179463895
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-24
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.491
• 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/S	None	None	0.954	N	0.777	0.404	0.33110744837	gnomAD-4.0.0	7.38521E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.79424E-05
P/T	None	None	0.954	N	0.795	0.425	0.362960570912	gnomAD-4.0.0	7.38521E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.40182E-07	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
P/A	0.0854	likely_benign	0.0776	benign	-0.825	Destabilizing	0.856	D	0.767	deleterious	N	0.480670721	None	None	N
P/C	0.4527	ambiguous	0.4362	ambiguous	-0.64	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
P/D	0.6064	likely_pathogenic	0.5664	pathogenic	-0.481	Destabilizing	0.982	D	0.859	deleterious	None	None	None	None	N
P/E	0.3164	likely_benign	0.2971	benign	-0.548	Destabilizing	0.965	D	0.802	deleterious	None	None	None	None	N
P/F	0.5656	likely_pathogenic	0.5573	ambiguous	-0.752	Destabilizing	0.998	D	0.92	deleterious	None	None	None	None	N
P/G	0.376	ambiguous	0.3586	ambiguous	-1.042	Destabilizing	0.965	D	0.815	deleterious	None	None	None	None	N
P/H	0.282	likely_benign	0.2778	benign	-0.491	Destabilizing	0.994	D	0.913	deleterious	N	0.511652218	None	None	N
P/I	0.3057	likely_benign	0.2751	benign	-0.374	Destabilizing	0.982	D	0.907	deleterious	None	None	None	None	N
P/K	0.2679	likely_benign	0.2496	benign	-0.673	Destabilizing	0.797	D	0.823	deleterious	None	None	None	None	N
P/L	0.1346	likely_benign	0.1352	benign	-0.374	Destabilizing	0.954	D	0.861	deleterious	N	0.491773536	None	None	N
P/M	0.2917	likely_benign	0.2749	benign	-0.375	Destabilizing	0.998	D	0.908	deleterious	None	None	None	None	N
P/N	0.4469	ambiguous	0.3981	ambiguous	-0.407	Destabilizing	0.965	D	0.872	deleterious	None	None	None	None	N
P/Q	0.2074	likely_benign	0.2005	benign	-0.625	Destabilizing	0.965	D	0.854	deleterious	None	None	None	None	N
P/R	0.1946	likely_benign	0.1963	benign	-0.125	Destabilizing	0.041	N	0.547	neutral	D	0.522501544	None	None	N
P/S	0.1945	likely_benign	0.1715	benign	-0.851	Destabilizing	0.954	D	0.777	deleterious	N	0.489304774	None	None	N
P/T	0.126	likely_benign	0.105	benign	-0.811	Destabilizing	0.954	D	0.795	deleterious	N	0.486747107	None	None	N
P/V	0.1915	likely_benign	0.1693	benign	-0.488	Destabilizing	0.982	D	0.879	deleterious	None	None	None	None	N
P/W	0.6693	likely_pathogenic	0.6941	pathogenic	-0.855	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
P/Y	0.5329	ambiguous	0.5286	ambiguous	-0.565	Destabilizing	0.998	D	0.913	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.