TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5021	15286;15287;15288	chr2:178734863;178734862;178734861	chr2:179599590;179599589;179599588
N2AB	4704	14335;14336;14337	chr2:178734863;178734862;178734861	chr2:179599590;179599589;179599588
N2A	3777	11554;11555;11556	chr2:178734863;178734862;178734861	chr2:179599590;179599589;179599588
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-33
• Domain position: 41
• Structural Position: 56
• Q(SASA): 0.4516
• 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	rs727503651	-0.577	0.801	N	0.387	0.113	0.314417295294	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	2.03169E-04	None	0	0	None	0	None	0	0	0
E/D	rs727503651	-0.577	0.801	N	0.387	0.113	0.314417295294	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	6.55E-05	0	0	0	None	0	0	0	0	0
E/D	rs727503651	-0.577	0.801	N	0.387	0.113	0.314417295294	gnomAD-4.0.0	1.40938E-05	None	None	None	None	N	None	1.69113E-05	1.52604E-04	None	0	0	None	0	0	0	0	2.84527E-05
E/K	rs779917005	0.218	0.012	N	0.244	0.198	0.346315397577	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	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	0.1344	likely_benign	0.1256	benign	-0.545	Destabilizing	0.012	N	0.193	neutral	N	0.508801056	None	None	N
E/C	0.8883	likely_pathogenic	0.8807	pathogenic	-0.342	Destabilizing	0.998	D	0.49	neutral	None	None	None	None	N
E/D	0.3069	likely_benign	0.2939	benign	-0.518	Destabilizing	0.801	D	0.387	neutral	N	0.505694657	None	None	N
E/F	0.8023	likely_pathogenic	0.7971	pathogenic	0.023	Stabilizing	0.974	D	0.466	neutral	None	None	None	None	N
E/G	0.2806	likely_benign	0.2537	benign	-0.822	Destabilizing	0.669	D	0.403	neutral	D	0.549807926	None	None	N
E/H	0.6298	likely_pathogenic	0.5906	pathogenic	0.286	Stabilizing	0.998	D	0.388	neutral	None	None	None	None	N
E/I	0.2637	likely_benign	0.2646	benign	0.184	Stabilizing	0.904	D	0.44	neutral	None	None	None	None	N
E/K	0.1959	likely_benign	0.1489	benign	0.122	Stabilizing	0.012	N	0.244	neutral	N	0.506468355	None	None	N
E/L	0.3218	likely_benign	0.3031	benign	0.184	Stabilizing	0.728	D	0.424	neutral	None	None	None	None	N
E/M	0.3761	ambiguous	0.3678	ambiguous	0.222	Stabilizing	0.993	D	0.446	neutral	None	None	None	None	N
E/N	0.4424	ambiguous	0.4217	ambiguous	-0.503	Destabilizing	0.949	D	0.393	neutral	None	None	None	None	N
E/P	0.2958	likely_benign	0.2707	benign	-0.038	Destabilizing	0.016	N	0.206	neutral	None	None	None	None	N
E/Q	0.1489	likely_benign	0.13	benign	-0.399	Destabilizing	0.934	D	0.41	neutral	N	0.50893731	None	None	N
E/R	0.356	ambiguous	0.28	benign	0.511	Stabilizing	0.904	D	0.376	neutral	None	None	None	None	N
E/S	0.3216	likely_benign	0.3096	benign	-0.68	Destabilizing	0.728	D	0.361	neutral	None	None	None	None	N
E/T	0.2871	likely_benign	0.2781	benign	-0.437	Destabilizing	0.842	D	0.387	neutral	None	None	None	None	N
E/V	0.1507	likely_benign	0.146	benign	-0.038	Destabilizing	0.051	N	0.253	neutral	N	0.510474712	None	None	N
E/W	0.9453	likely_pathogenic	0.9431	pathogenic	0.322	Stabilizing	0.998	D	0.585	neutral	None	None	None	None	N
E/Y	0.6934	likely_pathogenic	0.6934	pathogenic	0.307	Stabilizing	0.991	D	0.459	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.