TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30412	91459;91460;91461	chr2:178551666;178551665;178551664	chr2:179416393;179416392;179416391
N2AB	28771	86536;86537;86538	chr2:178551666;178551665;178551664	chr2:179416393;179416392;179416391
N2A	27844	83755;83756;83757	chr2:178551666;178551665;178551664	chr2:179416393;179416392;179416391
N2B	21347	64264;64265;64266	chr2:178551666;178551665;178551664	chr2:179416393;179416392;179416391
Novex-1	21472	64639;64640;64641	chr2:178551666;178551665;178551664	chr2:179416393;179416392;179416391
Novex-2	21539	64840;64841;64842	chr2:178551666;178551665;178551664	chr2:179416393;179416392;179416391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-109
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.7219
• 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
D/G	None	None	0.799	N	0.656	0.26	0.221734844693	gnomAD-4.0.0	1.6231E-06	None	None	None	None	I	None	5.82208E-05	0	None	0	0	None	0	0	0	0	0
D/N	None	None	0.799	N	0.559	0.252	0.232513804876	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.1481	likely_benign	0.174	benign	-0.404	Destabilizing	0.799	D	0.679	prob.neutral	N	0.427163364	None	None	I
D/C	0.5878	likely_pathogenic	0.6306	pathogenic	-0.081	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	I
D/E	0.0892	likely_benign	0.0935	benign	-0.387	Destabilizing	0.002	N	0.128	neutral	N	0.415444861	None	None	I
D/F	0.4618	ambiguous	0.5224	ambiguous	-0.252	Destabilizing	0.991	D	0.869	deleterious	None	None	None	None	I
D/G	0.235	likely_benign	0.2806	benign	-0.616	Destabilizing	0.799	D	0.656	prob.neutral	N	0.481517924	None	None	I
D/H	0.2995	likely_benign	0.3443	ambiguous	-0.1	Destabilizing	0.966	D	0.761	deleterious	N	0.508896526	None	None	I
D/I	0.2147	likely_benign	0.2619	benign	0.113	Stabilizing	0.974	D	0.868	deleterious	None	None	None	None	I
D/K	0.347	ambiguous	0.3926	ambiguous	0.197	Stabilizing	0.725	D	0.627	neutral	None	None	None	None	I
D/L	0.2432	likely_benign	0.2795	benign	0.113	Stabilizing	0.949	D	0.72	deleterious	None	None	None	None	I
D/M	0.423	ambiguous	0.4698	ambiguous	0.277	Stabilizing	0.998	D	0.842	deleterious	None	None	None	None	I
D/N	0.1183	likely_benign	0.1452	benign	-0.177	Destabilizing	0.799	D	0.559	neutral	N	0.481171207	None	None	I
D/P	0.4431	ambiguous	0.4815	ambiguous	-0.037	Destabilizing	0.974	D	0.724	deleterious	None	None	None	None	I
D/Q	0.2644	likely_benign	0.2946	benign	-0.137	Destabilizing	0.725	D	0.62	neutral	None	None	None	None	I
D/R	0.4165	ambiguous	0.4628	ambiguous	0.402	Stabilizing	0.949	D	0.737	deleterious	None	None	None	None	I
D/S	0.1259	likely_benign	0.146	benign	-0.285	Destabilizing	0.841	D	0.549	neutral	None	None	None	None	I
D/T	0.2036	likely_benign	0.2454	benign	-0.116	Destabilizing	0.841	D	0.713	prob.delet.	None	None	None	None	I
D/V	0.145	likely_benign	0.1744	benign	-0.037	Destabilizing	0.966	D	0.739	deleterious	N	0.483864796	None	None	I
D/W	0.8803	likely_pathogenic	0.8923	pathogenic	-0.079	Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	I
D/Y	0.22	likely_benign	0.2464	benign	-0.009	Destabilizing	0.989	D	0.872	deleterious	N	0.465858148	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.