TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27439	82540;82541;82542	chr2:178563817;178563816;178563815	chr2:179428544;179428543;179428542
N2AB	25798	77617;77618;77619	chr2:178563817;178563816;178563815	chr2:179428544;179428543;179428542
N2A	24871	74836;74837;74838	chr2:178563817;178563816;178563815	chr2:179428544;179428543;179428542
N2B	18374	55345;55346;55347	chr2:178563817;178563816;178563815	chr2:179428544;179428543;179428542
Novex-1	18499	55720;55721;55722	chr2:178563817;178563816;178563815	chr2:179428544;179428543;179428542
Novex-2	18566	55921;55922;55923	chr2:178563817;178563816;178563815	chr2:179428544;179428543;179428542
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-87
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3893
• 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
E/K	rs748460030	-0.551	0.892	N	0.503	0.3	0.357519025918	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs748460030	-0.551	0.892	N	0.503	0.3	0.357519025918	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.25E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs748460030	-0.551	0.892	N	0.503	0.3	0.357519025918	gnomAD-4.0.0	3.0987E-06	None	None	None	None	N	None	4.00662E-05	0	None	0	0	None	0	0	1.69527E-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
E/A	0.5384	ambiguous	0.5317	ambiguous	-1.151	Destabilizing	0.805	D	0.547	neutral	N	0.480967571	None	None	N
E/C	0.9715	likely_pathogenic	0.9691	pathogenic	-0.545	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/D	0.5919	likely_pathogenic	0.6289	pathogenic	-1.166	Destabilizing	0.892	D	0.413	neutral	N	0.48276477	None	None	N
E/F	0.9835	likely_pathogenic	0.9841	pathogenic	-0.685	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
E/G	0.6917	likely_pathogenic	0.7058	pathogenic	-1.532	Destabilizing	0.025	N	0.385	neutral	N	0.494236434	None	None	N
E/H	0.9008	likely_pathogenic	0.9008	pathogenic	-0.98	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/I	0.8123	likely_pathogenic	0.8132	pathogenic	-0.096	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
E/K	0.5232	ambiguous	0.5296	ambiguous	-0.752	Destabilizing	0.892	D	0.503	neutral	N	0.469229191	None	None	N
E/L	0.8925	likely_pathogenic	0.8965	pathogenic	-0.096	Destabilizing	0.987	D	0.799	deleterious	None	None	None	None	N
E/M	0.862	likely_pathogenic	0.8648	pathogenic	0.512	Stabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
E/N	0.7731	likely_pathogenic	0.7798	pathogenic	-1.186	Destabilizing	0.975	D	0.661	neutral	None	None	None	None	N
E/P	0.9773	likely_pathogenic	0.9782	pathogenic	-0.428	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
E/Q	0.3343	likely_benign	0.3304	benign	-1.046	Destabilizing	0.994	D	0.628	neutral	N	0.467280634	None	None	N
E/R	0.6776	likely_pathogenic	0.6749	pathogenic	-0.545	Destabilizing	0.987	D	0.691	prob.neutral	None	None	None	None	N
E/S	0.6138	likely_pathogenic	0.6174	pathogenic	-1.599	Destabilizing	0.916	D	0.513	neutral	None	None	None	None	N
E/T	0.6274	likely_pathogenic	0.6242	pathogenic	-1.27	Destabilizing	0.987	D	0.748	deleterious	None	None	None	None	N
E/V	0.6663	likely_pathogenic	0.6646	pathogenic	-0.428	Destabilizing	0.983	D	0.793	deleterious	N	0.479841935	None	None	N
E/W	0.9952	likely_pathogenic	0.9955	pathogenic	-0.432	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
E/Y	0.9679	likely_pathogenic	0.9676	pathogenic	-0.415	Destabilizing	0.996	D	0.791	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.