TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18902	56929;56930;56931	chr2:178599006;178599005;178599004	chr2:179463733;179463732;179463731
N2AB	17261	52006;52007;52008	chr2:178599006;178599005;178599004	chr2:179463733;179463732;179463731
N2A	16334	49225;49226;49227	chr2:178599006;178599005;178599004	chr2:179463733;179463732;179463731
N2B	9837	29734;29735;29736	chr2:178599006;178599005;178599004	chr2:179463733;179463732;179463731
Novex-1	9962	30109;30110;30111	chr2:178599006;178599005;178599004	chr2:179463733;179463732;179463731
Novex-2	10029	30310;30311;30312	chr2:178599006;178599005;178599004	chr2:179463733;179463732;179463731
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-25
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1838
• 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
T/I	None	None	1.0	N	0.725	0.422	0.538283067721	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
T/A	0.3005	likely_benign	0.2366	benign	-1.037	Destabilizing	0.999	D	0.567	neutral	N	0.483689823	None	None	N
T/C	0.7846	likely_pathogenic	0.6934	pathogenic	-1.042	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
T/D	0.8594	likely_pathogenic	0.8166	pathogenic	-1.171	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
T/E	0.7835	likely_pathogenic	0.6985	pathogenic	-1.123	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/F	0.649	likely_pathogenic	0.5736	pathogenic	-1.26	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
T/G	0.7938	likely_pathogenic	0.7222	pathogenic	-1.299	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
T/H	0.7181	likely_pathogenic	0.644	pathogenic	-1.63	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/I	0.3222	likely_benign	0.2155	benign	-0.414	Destabilizing	1.0	D	0.725	prob.delet.	N	0.483943312	None	None	N
T/K	0.7728	likely_pathogenic	0.6714	pathogenic	-0.788	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/L	0.2657	likely_benign	0.1733	benign	-0.414	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
T/M	0.1495	likely_benign	0.1249	benign	-0.117	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/N	0.4504	ambiguous	0.3917	ambiguous	-1.059	Destabilizing	1.0	D	0.664	neutral	N	0.474891185	None	None	N
T/P	0.9521	likely_pathogenic	0.936	pathogenic	-0.592	Destabilizing	1.0	D	0.729	prob.delet.	N	0.517709513	None	None	N
T/Q	0.6618	likely_pathogenic	0.5642	pathogenic	-1.251	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/R	0.7364	likely_pathogenic	0.6407	pathogenic	-0.586	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/S	0.3836	ambiguous	0.3485	ambiguous	-1.272	Destabilizing	0.999	D	0.554	neutral	N	0.466190998	None	None	N
T/V	0.2205	likely_benign	0.1548	benign	-0.592	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
T/W	0.8681	likely_pathogenic	0.8311	pathogenic	-1.217	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/Y	0.706	likely_pathogenic	0.6048	pathogenic	-0.903	Destabilizing	1.0	D	0.763	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.