TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21345	64258;64259;64260	chr2:178587178;178587177;178587176	chr2:179451905;179451904;179451903
N2AB	19704	59335;59336;59337	chr2:178587178;178587177;178587176	chr2:179451905;179451904;179451903
N2A	18777	56554;56555;56556	chr2:178587178;178587177;178587176	chr2:179451905;179451904;179451903
N2B	12280	37063;37064;37065	chr2:178587178;178587177;178587176	chr2:179451905;179451904;179451903
Novex-1	12405	37438;37439;37440	chr2:178587178;178587177;178587176	chr2:179451905;179451904;179451903
Novex-2	12472	37639;37640;37641	chr2:178587178;178587177;178587176	chr2:179451905;179451904;179451903
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: Fn3-42
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.4594
• 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
E/K	rs776495338	0.594	0.438	N	0.205	0.253	0.225215365344	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	3.27E-05	None	9.28E-05	0	1.65673E-04
E/K	rs776495338	0.594	0.438	N	0.205	0.253	0.225215365344	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs776495338	0.594	0.438	N	0.205	0.253	0.225215365344	gnomAD-4.0.0	1.42579E-05	None	None	None	None	I	None	9.35354E-05	0	None	0	0	None	3.12383E-05	0	9.32641E-06	3.29417E-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
E/A	0.2213	likely_benign	0.2588	benign	-0.508	Destabilizing	0.961	D	0.539	neutral	N	0.4574117	None	None	I
E/C	0.8879	likely_pathogenic	0.9212	pathogenic	-0.193	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
E/D	0.1848	likely_benign	0.2194	benign	-0.405	Destabilizing	0.98	D	0.432	neutral	N	0.437633861	None	None	I
E/F	0.904	likely_pathogenic	0.934	pathogenic	-0.289	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
E/G	0.3747	ambiguous	0.4446	ambiguous	-0.697	Destabilizing	0.98	D	0.569	neutral	N	0.504679998	None	None	I
E/H	0.6648	likely_pathogenic	0.735	pathogenic	0.098	Stabilizing	0.999	D	0.4	neutral	None	None	None	None	I
E/I	0.3941	ambiguous	0.4561	ambiguous	-0.042	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
E/K	0.218	likely_benign	0.2811	benign	0.303	Stabilizing	0.438	N	0.205	neutral	N	0.411332694	None	None	I
E/L	0.5538	ambiguous	0.626	pathogenic	-0.042	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	I
E/M	0.565	likely_pathogenic	0.6442	pathogenic	0.022	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	I
E/N	0.375	ambiguous	0.4544	ambiguous	-0.161	Destabilizing	0.985	D	0.438	neutral	None	None	None	None	I
E/P	0.7193	likely_pathogenic	0.6866	pathogenic	-0.178	Destabilizing	0.999	D	0.5	neutral	None	None	None	None	I
E/Q	0.1848	likely_benign	0.2154	benign	-0.108	Destabilizing	0.984	D	0.429	neutral	N	0.472015793	None	None	I
E/R	0.3961	ambiguous	0.4707	ambiguous	0.574	Stabilizing	0.942	D	0.457	neutral	None	None	None	None	I
E/S	0.3084	likely_benign	0.3715	ambiguous	-0.285	Destabilizing	0.97	D	0.477	neutral	None	None	None	None	I
E/T	0.2901	likely_benign	0.3488	ambiguous	-0.117	Destabilizing	0.985	D	0.523	neutral	None	None	None	None	I
E/V	0.2865	likely_benign	0.3343	benign	-0.178	Destabilizing	0.994	D	0.516	neutral	N	0.490948271	None	None	I
E/W	0.9781	likely_pathogenic	0.9858	pathogenic	-0.083	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/Y	0.8289	likely_pathogenic	0.874	pathogenic	-0.033	Destabilizing	0.999	D	0.636	neutral	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.