TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19863	59812;59813;59814	chr2:178592418;178592417;178592416	chr2:179457145;179457144;179457143
N2AB	18222	54889;54890;54891	chr2:178592418;178592417;178592416	chr2:179457145;179457144;179457143
N2A	17295	52108;52109;52110	chr2:178592418;178592417;178592416	chr2:179457145;179457144;179457143
N2B	10798	32617;32618;32619	chr2:178592418;178592417;178592416	chr2:179457145;179457144;179457143
Novex-1	10923	32992;32993;32994	chr2:178592418;178592417;178592416	chr2:179457145;179457144;179457143
Novex-2	10990	33193;33194;33195	chr2:178592418;178592417;178592416	chr2:179457145;179457144;179457143
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-119
• Domain position: 74
• Structural Position: 163
• Q(SASA): 0.6354
• 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
A/D	rs1416865059	-0.243	1.0	D	0.801	0.568	0.619908932184	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
A/D	rs1416865059	-0.243	1.0	D	0.801	0.568	0.619908932184	gnomAD-4.0.0	1.59233E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43488E-05	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
A/C	0.5161	ambiguous	0.5197	ambiguous	-0.888	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/D	0.8449	likely_pathogenic	0.8605	pathogenic	-0.533	Destabilizing	1.0	D	0.801	deleterious	D	0.531490534	None	None	I
A/E	0.7517	likely_pathogenic	0.7734	pathogenic	-0.676	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/F	0.6164	likely_pathogenic	0.6095	pathogenic	-0.977	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
A/G	0.3156	likely_benign	0.2962	benign	-0.288	Destabilizing	1.0	D	0.602	neutral	D	0.529365878	None	None	I
A/H	0.7815	likely_pathogenic	0.8147	pathogenic	-0.271	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
A/I	0.4564	ambiguous	0.4421	ambiguous	-0.493	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
A/K	0.8793	likely_pathogenic	0.9034	pathogenic	-0.55	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/L	0.4684	ambiguous	0.4789	ambiguous	-0.493	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
A/M	0.4626	ambiguous	0.4628	ambiguous	-0.634	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
A/N	0.7119	likely_pathogenic	0.7143	pathogenic	-0.274	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
A/P	0.9463	likely_pathogenic	0.9524	pathogenic	-0.404	Destabilizing	1.0	D	0.748	deleterious	D	0.543011424	None	None	I
A/Q	0.7072	likely_pathogenic	0.7501	pathogenic	-0.517	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
A/R	0.8054	likely_pathogenic	0.8445	pathogenic	-0.147	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
A/S	0.1434	likely_benign	0.1339	benign	-0.467	Destabilizing	1.0	D	0.636	neutral	D	0.530365956	None	None	I
A/T	0.2431	likely_benign	0.2364	benign	-0.539	Destabilizing	1.0	D	0.717	prob.delet.	N	0.510255499	None	None	I
A/V	0.1989	likely_benign	0.1855	benign	-0.404	Destabilizing	1.0	D	0.68	prob.neutral	N	0.511201405	None	None	I
A/W	0.9427	likely_pathogenic	0.9514	pathogenic	-1.059	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
A/Y	0.7794	likely_pathogenic	0.8025	pathogenic	-0.764	Destabilizing	1.0	D	0.795	deleterious	None	None	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.