TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34259	103000;103001;103002	chr2:178533840;178533839;178533838	chr2:179398567;179398566;179398565
N2AB	32618	98077;98078;98079	chr2:178533840;178533839;178533838	chr2:179398567;179398566;179398565
N2A	31691	95296;95297;95298	chr2:178533840;178533839;178533838	chr2:179398567;179398566;179398565
N2B	25194	75805;75806;75807	chr2:178533840;178533839;178533838	chr2:179398567;179398566;179398565
Novex-1	25319	76180;76181;76182	chr2:178533840;178533839;178533838	chr2:179398567;179398566;179398565
Novex-2	25386	76381;76382;76383	chr2:178533840;178533839;178533838	chr2:179398567;179398566;179398565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-161
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6515
• 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	rs1301566986	None	0.977	N	0.503	0.367	0.366085729538	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1301566986	None	0.977	N	0.503	0.367	0.366085729538	gnomAD-4.0.0	1.23928E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69509E-06	0	0
E/Q	None	None	0.997	N	0.627	0.285	0.463328977263	gnomAD-4.0.0	6.84161E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99408E-07	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	0.4334	ambiguous	0.4551	ambiguous	-0.558	Destabilizing	0.977	D	0.577	neutral	N	0.511990839	None	None	N
E/C	0.964	likely_pathogenic	0.9676	pathogenic	-0.316	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/D	0.5256	ambiguous	0.5823	pathogenic	-0.637	Destabilizing	0.898	D	0.452	neutral	N	0.509451966	None	None	N
E/F	0.9537	likely_pathogenic	0.9695	pathogenic	-0.064	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/G	0.6821	likely_pathogenic	0.6952	pathogenic	-0.846	Destabilizing	0.955	D	0.544	neutral	N	0.488645752	None	None	N
E/H	0.8714	likely_pathogenic	0.8903	pathogenic	0.045	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	N
E/I	0.7308	likely_pathogenic	0.7761	pathogenic	0.201	Stabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
E/K	0.5638	ambiguous	0.5863	pathogenic	-0.038	Destabilizing	0.977	D	0.503	neutral	N	0.459964508	None	None	N
E/L	0.823	likely_pathogenic	0.8618	pathogenic	0.201	Stabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
E/M	0.799	likely_pathogenic	0.8577	pathogenic	0.309	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/N	0.7772	likely_pathogenic	0.8148	pathogenic	-0.555	Destabilizing	0.289	N	0.266	neutral	None	None	None	None	N
E/P	0.9897	likely_pathogenic	0.9674	pathogenic	-0.03	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
E/Q	0.3508	ambiguous	0.3881	ambiguous	-0.449	Destabilizing	0.997	D	0.627	neutral	N	0.49080749	None	None	N
E/R	0.6507	likely_pathogenic	0.668	pathogenic	0.307	Stabilizing	0.995	D	0.648	neutral	None	None	None	None	N
E/S	0.5761	likely_pathogenic	0.6176	pathogenic	-0.749	Destabilizing	0.966	D	0.524	neutral	None	None	None	None	N
E/T	0.6063	likely_pathogenic	0.6499	pathogenic	-0.506	Destabilizing	0.995	D	0.658	neutral	None	None	None	None	N
E/V	0.5059	ambiguous	0.5738	pathogenic	-0.03	Destabilizing	0.997	D	0.661	neutral	N	0.491556851	None	None	N
E/W	0.989	likely_pathogenic	0.991	pathogenic	0.194	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/Y	0.9281	likely_pathogenic	0.9412	pathogenic	0.2	Stabilizing	0.999	D	0.673	neutral	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.