TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7765	23518;23519;23520	chr2:178720469;178720468;178720467	chr2:179585196;179585195;179585194
N2AB	7448	22567;22568;22569	chr2:178720469;178720468;178720467	chr2:179585196;179585195;179585194
N2A	6521	19786;19787;19788	chr2:178720469;178720468;178720467	chr2:179585196;179585195;179585194
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-62
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.369
• 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/D	rs774259283	-0.356	0.001	N	0.121	0.107	0.0482279557977	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
E/D	rs774259283	-0.356	0.001	N	0.121	0.107	0.0482279557977	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs774259283	-0.356	0.001	N	0.121	0.107	0.0482279557977	gnomAD-4.0.0	3.09867E-06	None	None	None	None	N	None	5.33988E-05	0	None	0	0	None	1.56196E-05	0	0	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	0.2478	likely_benign	0.3004	benign	-0.756	Destabilizing	0.013	N	0.151	neutral	N	0.513396348	None	None	N
E/C	0.9183	likely_pathogenic	0.94	pathogenic	-0.227	Destabilizing	0.991	D	0.375	neutral	None	None	None	None	N
E/D	0.098	likely_benign	0.1137	benign	-0.806	Destabilizing	0.001	N	0.121	neutral	N	0.4540414	None	None	N
E/F	0.8424	likely_pathogenic	0.8781	pathogenic	-0.284	Destabilizing	0.965	D	0.389	neutral	None	None	None	None	N
E/G	0.2431	likely_benign	0.2979	benign	-1.072	Destabilizing	0.001	N	0.145	neutral	N	0.515340575	None	None	N
E/H	0.6362	likely_pathogenic	0.6861	pathogenic	-0.347	Destabilizing	0.965	D	0.333	neutral	None	None	None	None	N
E/I	0.5766	likely_pathogenic	0.6206	pathogenic	0.091	Stabilizing	0.901	D	0.414	neutral	None	None	None	None	N
E/K	0.3876	ambiguous	0.4294	ambiguous	-0.101	Destabilizing	0.166	N	0.249	neutral	N	0.468277347	None	None	N
E/L	0.5291	ambiguous	0.5721	pathogenic	0.091	Stabilizing	0.561	D	0.416	neutral	None	None	None	None	N
E/M	0.6284	likely_pathogenic	0.6706	pathogenic	0.469	Stabilizing	0.991	D	0.353	neutral	None	None	None	None	N
E/N	0.3198	likely_benign	0.3881	ambiguous	-0.667	Destabilizing	0.39	N	0.213	neutral	None	None	None	None	N
E/P	0.9114	likely_pathogenic	0.9404	pathogenic	-0.17	Destabilizing	0.901	D	0.367	neutral	None	None	None	None	N
E/Q	0.234	likely_benign	0.2566	benign	-0.545	Destabilizing	0.491	N	0.334	neutral	N	0.484516236	None	None	N
E/R	0.5216	ambiguous	0.5616	ambiguous	0.162	Stabilizing	0.004	N	0.215	neutral	None	None	None	None	N
E/S	0.2774	likely_benign	0.3351	benign	-0.881	Destabilizing	0.209	N	0.245	neutral	None	None	None	None	N
E/T	0.3282	likely_benign	0.3835	ambiguous	-0.608	Destabilizing	0.561	D	0.325	neutral	None	None	None	None	N
E/V	0.3486	ambiguous	0.3822	ambiguous	-0.17	Destabilizing	0.491	N	0.4	neutral	N	0.491444995	None	None	N
E/W	0.9567	likely_pathogenic	0.9694	pathogenic	-0.003	Destabilizing	0.991	D	0.437	neutral	None	None	None	None	N
E/Y	0.7762	likely_pathogenic	0.8271	pathogenic	-0.011	Destabilizing	0.965	D	0.363	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.