TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31604	95035;95036;95037	chr2:178546618;178546617;178546616	chr2:179411345;179411344;179411343
N2AB	29963	90112;90113;90114	chr2:178546618;178546617;178546616	chr2:179411345;179411344;179411343
N2A	29036	87331;87332;87333	chr2:178546618;178546617;178546616	chr2:179411345;179411344;179411343
N2B	22539	67840;67841;67842	chr2:178546618;178546617;178546616	chr2:179411345;179411344;179411343
Novex-1	22664	68215;68216;68217	chr2:178546618;178546617;178546616	chr2:179411345;179411344;179411343
Novex-2	22731	68416;68417;68418	chr2:178546618;178546617;178546616	chr2:179411345;179411344;179411343
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: Fn3-118
• Domain position: 99
• Structural Position: 129
• Q(SASA): 0.3573
• 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/A	None	None	0.022	N	0.296	0.121	0.188950314367	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
T/P	None	None	0.981	N	0.694	0.279	0.485776496936	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
T/A	0.0939	likely_benign	0.0871	benign	-0.59	Destabilizing	0.022	N	0.296	neutral	N	0.494447149	None	None	N
T/C	0.4234	ambiguous	0.4156	ambiguous	-0.383	Destabilizing	0.996	D	0.655	prob.neutral	None	None	None	None	N
T/D	0.5276	ambiguous	0.5405	ambiguous	0.068	Stabilizing	0.985	D	0.637	neutral	None	None	None	None	N
T/E	0.3649	ambiguous	0.3748	ambiguous	0.025	Stabilizing	0.971	D	0.603	neutral	None	None	None	None	N
T/F	0.2314	likely_benign	0.2233	benign	-0.865	Destabilizing	0.971	D	0.794	deleterious	None	None	None	None	N
T/G	0.3837	ambiguous	0.3608	ambiguous	-0.786	Destabilizing	0.825	D	0.625	neutral	None	None	None	None	N
T/H	0.2867	likely_benign	0.2778	benign	-1.102	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
T/I	0.0957	likely_benign	0.0961	benign	-0.178	Destabilizing	0.049	N	0.313	neutral	N	0.392456145	None	None	N
T/K	0.2558	likely_benign	0.254	benign	-0.559	Destabilizing	0.971	D	0.597	neutral	None	None	None	None	N
T/L	0.0844	likely_benign	0.0811	benign	-0.178	Destabilizing	0.66	D	0.519	neutral	None	None	None	None	N
T/M	0.0872	likely_benign	0.0864	benign	0.064	Stabilizing	0.992	D	0.665	prob.neutral	None	None	None	None	N
T/N	0.1701	likely_benign	0.1651	benign	-0.4	Destabilizing	0.981	D	0.621	neutral	N	0.520844316	None	None	N
T/P	0.154	likely_benign	0.1383	benign	-0.284	Destabilizing	0.981	D	0.694	prob.delet.	N	0.51416906	None	None	N
T/Q	0.2311	likely_benign	0.2262	benign	-0.614	Destabilizing	0.985	D	0.661	prob.neutral	None	None	None	None	N
T/R	0.2078	likely_benign	0.1982	benign	-0.298	Destabilizing	0.985	D	0.694	prob.delet.	None	None	None	None	N
T/S	0.141	likely_benign	0.1332	benign	-0.66	Destabilizing	0.78	D	0.515	neutral	N	0.512262119	None	None	N
T/V	0.0894	likely_benign	0.0891	benign	-0.284	Destabilizing	0.66	D	0.475	neutral	None	None	None	None	N
T/W	0.6552	likely_pathogenic	0.6257	pathogenic	-0.811	Destabilizing	0.999	D	0.7	prob.delet.	None	None	None	None	N
T/Y	0.3146	likely_benign	0.3018	benign	-0.565	Destabilizing	0.995	D	0.812	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.