TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26858	80797;80798;80799	chr2:178565560;178565559;178565558	chr2:179430287;179430286;179430285
N2AB	25217	75874;75875;75876	chr2:178565560;178565559;178565558	chr2:179430287;179430286;179430285
N2A	24290	73093;73094;73095	chr2:178565560;178565559;178565558	chr2:179430287;179430286;179430285
N2B	17793	53602;53603;53604	chr2:178565560;178565559;178565558	chr2:179430287;179430286;179430285
Novex-1	17918	53977;53978;53979	chr2:178565560;178565559;178565558	chr2:179430287;179430286;179430285
Novex-2	17985	54178;54179;54180	chr2:178565560;178565559;178565558	chr2:179430287;179430286;179430285
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: Fn3-83
• Domain position: 79
• Structural Position: 113
• Q(SASA): 0.4847
• 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	None	None	0.888	N	0.48	0.274	0.281780670237	gnomAD-4.0.0	4.79003E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29699E-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	0.3737	ambiguous	0.3651	ambiguous	-0.518	Destabilizing	0.678	D	0.477	neutral	N	0.414044925	None	None	N
E/C	0.959	likely_pathogenic	0.9595	pathogenic	-0.064	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
E/D	0.1844	likely_benign	0.1583	benign	-0.4	Destabilizing	0.627	D	0.355	neutral	N	0.432516043	None	None	N
E/F	0.9446	likely_pathogenic	0.9363	pathogenic	-0.314	Destabilizing	0.948	D	0.613	neutral	None	None	None	None	N
E/G	0.3894	ambiguous	0.3778	ambiguous	-0.742	Destabilizing	0.98	D	0.469	neutral	N	0.486094238	None	None	N
E/H	0.7865	likely_pathogenic	0.7815	pathogenic	-0.191	Destabilizing	0.997	D	0.509	neutral	None	None	None	None	N
E/I	0.6173	likely_pathogenic	0.6091	pathogenic	0.046	Stabilizing	0.017	N	0.54	neutral	None	None	None	None	N
E/K	0.4024	ambiguous	0.4095	ambiguous	0.272	Stabilizing	0.888	D	0.48	neutral	N	0.417797306	None	None	N
E/L	0.7047	likely_pathogenic	0.702	pathogenic	0.046	Stabilizing	0.294	N	0.518	neutral	None	None	None	None	N
E/M	0.7579	likely_pathogenic	0.7525	pathogenic	0.229	Stabilizing	0.852	D	0.559	neutral	None	None	None	None	N
E/N	0.5475	ambiguous	0.53	ambiguous	-0.117	Destabilizing	0.961	D	0.518	neutral	None	None	None	None	N
E/P	0.8438	likely_pathogenic	0.8481	pathogenic	-0.122	Destabilizing	0.886	D	0.507	neutral	None	None	None	None	N
E/Q	0.2948	likely_benign	0.3033	benign	-0.067	Destabilizing	0.984	D	0.476	neutral	N	0.463935028	None	None	N
E/R	0.5891	likely_pathogenic	0.5938	pathogenic	0.458	Stabilizing	0.991	D	0.516	neutral	None	None	None	None	N
E/S	0.4288	ambiguous	0.4157	ambiguous	-0.284	Destabilizing	0.85	D	0.486	neutral	None	None	None	None	N
E/T	0.5383	ambiguous	0.5238	ambiguous	-0.096	Destabilizing	0.931	D	0.477	neutral	None	None	None	None	N
E/V	0.444	ambiguous	0.439	ambiguous	-0.122	Destabilizing	0.183	N	0.459	neutral	N	0.445426625	None	None	N
E/W	0.9803	likely_pathogenic	0.9754	pathogenic	-0.116	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
E/Y	0.8948	likely_pathogenic	0.8751	pathogenic	-0.058	Destabilizing	0.99	D	0.569	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.