TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25389	76390;76391;76392	chr2:178569967;178569966;178569965	chr2:179434694;179434693;179434692
N2AB	23748	71467;71468;71469	chr2:178569967;178569966;178569965	chr2:179434694;179434693;179434692
N2A	22821	68686;68687;68688	chr2:178569967;178569966;178569965	chr2:179434694;179434693;179434692
N2B	16324	49195;49196;49197	chr2:178569967;178569966;178569965	chr2:179434694;179434693;179434692
Novex-1	16449	49570;49571;49572	chr2:178569967;178569966;178569965	chr2:179434694;179434693;179434692
Novex-2	16516	49771;49772;49773	chr2:178569967;178569966;178569965	chr2:179434694;179434693;179434692
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: Fn3-72
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.6606
• 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/D	rs371435213	-0.039	0.447	N	0.431	0.115	0.297031009988	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
E/D	rs371435213	-0.039	0.447	N	0.431	0.115	0.297031009988	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs371435213	-0.039	0.447	N	0.431	0.115	0.297031009988	gnomAD-4.0.0	6.57834E-06	None	None	None	None	I	None	2.41359E-05	0	None	0	0	None	0	0	0	0	0
E/G	None	None	0.491	N	0.464	0.209	0.303453137403	gnomAD-4.0.0	1.59487E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86535E-06	0	0
E/K	None	None	0.005	N	0.151	0.113	0.229924730088	gnomAD-4.0.0	1.59537E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8662E-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	0.089	likely_benign	0.0903	benign	-0.469	Destabilizing	0.005	N	0.21	neutral	N	0.504685572	None	None	I
E/C	0.64	likely_pathogenic	0.6836	pathogenic	-0.053	Destabilizing	0.991	D	0.457	neutral	None	None	None	None	I
E/D	0.0957	likely_benign	0.1028	benign	-0.322	Destabilizing	0.447	N	0.431	neutral	N	0.487601321	None	None	I
E/F	0.5192	ambiguous	0.5335	ambiguous	-0.355	Destabilizing	0.965	D	0.473	neutral	None	None	None	None	I
E/G	0.1225	likely_benign	0.1212	benign	-0.648	Destabilizing	0.491	N	0.464	neutral	N	0.483863952	None	None	I
E/H	0.3247	likely_benign	0.3264	benign	-0.099	Destabilizing	0.965	D	0.508	neutral	None	None	None	None	I
E/I	0.1723	likely_benign	0.1915	benign	-0.036	Destabilizing	0.818	D	0.517	neutral	None	None	None	None	I
E/K	0.0859	likely_benign	0.0816	benign	0.35	Stabilizing	0.005	N	0.151	neutral	N	0.488428041	None	None	I
E/L	0.1783	likely_benign	0.1813	benign	-0.036	Destabilizing	0.561	D	0.487	neutral	None	None	None	None	I
E/M	0.2442	likely_benign	0.2538	benign	0.107	Stabilizing	0.965	D	0.469	neutral	None	None	None	None	I
E/N	0.1554	likely_benign	0.1644	benign	-0.014	Destabilizing	0.722	D	0.515	neutral	None	None	None	None	I
E/P	0.2528	likely_benign	0.2676	benign	-0.161	Destabilizing	0.004	N	0.271	neutral	None	None	None	None	I
E/Q	0.0975	likely_benign	0.0945	benign	0.021	Stabilizing	0.491	N	0.539	neutral	N	0.473613304	None	None	I
E/R	0.1675	likely_benign	0.1564	benign	0.518	Stabilizing	0.39	N	0.459	neutral	None	None	None	None	I
E/S	0.1245	likely_benign	0.127	benign	-0.151	Destabilizing	0.209	N	0.422	neutral	None	None	None	None	I
E/T	0.135	likely_benign	0.1426	benign	0.003	Stabilizing	0.007	N	0.2	neutral	None	None	None	None	I
E/V	0.1113	likely_benign	0.1166	benign	-0.161	Destabilizing	0.491	N	0.476	neutral	N	0.478650166	None	None	I
E/W	0.8155	likely_pathogenic	0.81	pathogenic	-0.189	Destabilizing	0.991	D	0.532	neutral	None	None	None	None	I
E/Y	0.4123	ambiguous	0.4309	ambiguous	-0.113	Destabilizing	0.965	D	0.485	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.