TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28492	85699;85700;85701	chr2:178560658;178560657;178560656	chr2:179425385;179425384;179425383
N2AB	26851	80776;80777;80778	chr2:178560658;178560657;178560656	chr2:179425385;179425384;179425383
N2A	25924	77995;77996;77997	chr2:178560658;178560657;178560656	chr2:179425385;179425384;179425383
N2B	19427	58504;58505;58506	chr2:178560658;178560657;178560656	chr2:179425385;179425384;179425383
Novex-1	19552	58879;58880;58881	chr2:178560658;178560657;178560656	chr2:179425385;179425384;179425383
Novex-2	19619	59080;59081;59082	chr2:178560658;178560657;178560656	chr2:179425385;179425384;179425383
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: Fn3-95
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.1542
• 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/G	None	None	0.988	N	0.695	0.529	0.615496883321	gnomAD-4.0.0	2.05284E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69841E-06	0	0
E/K	None	None	0.958	N	0.503	0.359	0.467585353272	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/Q	None	None	0.994	N	0.633	0.351	0.421184727016	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/V	rs771012463	-0.155	0.994	N	0.795	0.563	0.7378300549	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/V	rs771012463	-0.155	0.994	N	0.795	0.563	0.7378300549	gnomAD-4.0.0	1.36856E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79894E-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	0.5314	ambiguous	0.5955	pathogenic	-1.015	Destabilizing	0.958	D	0.593	neutral	N	0.495286391	None	None	N
E/C	0.9681	likely_pathogenic	0.9771	pathogenic	-0.739	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/D	0.4235	ambiguous	0.5032	ambiguous	-1.483	Destabilizing	0.067	N	0.185	neutral	N	0.476808325	None	None	N
E/F	0.978	likely_pathogenic	0.9846	pathogenic	-0.514	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/G	0.5675	likely_pathogenic	0.6387	pathogenic	-1.429	Destabilizing	0.988	D	0.695	prob.neutral	N	0.499592032	None	None	N
E/H	0.879	likely_pathogenic	0.9116	pathogenic	-0.981	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/I	0.8743	likely_pathogenic	0.915	pathogenic	0.139	Stabilizing	0.995	D	0.835	deleterious	None	None	None	None	N
E/K	0.4864	ambiguous	0.582	pathogenic	-1.4	Destabilizing	0.958	D	0.503	neutral	N	0.470305601	None	None	N
E/L	0.8472	likely_pathogenic	0.8876	pathogenic	0.139	Stabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
E/M	0.8475	likely_pathogenic	0.8842	pathogenic	0.765	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/N	0.7273	likely_pathogenic	0.8045	pathogenic	-1.735	Destabilizing	0.982	D	0.669	neutral	None	None	None	None	N
E/P	0.8881	likely_pathogenic	0.9048	pathogenic	-0.225	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
E/Q	0.371	ambiguous	0.4335	ambiguous	-1.509	Destabilizing	0.994	D	0.633	neutral	N	0.492030707	None	None	N
E/R	0.6587	likely_pathogenic	0.7351	pathogenic	-1.17	Destabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
E/S	0.6878	likely_pathogenic	0.7496	pathogenic	-2.188	Highly Destabilizing	0.968	D	0.539	neutral	None	None	None	None	N
E/T	0.8144	likely_pathogenic	0.8613	pathogenic	-1.844	Destabilizing	0.991	D	0.708	prob.delet.	None	None	None	None	N
E/V	0.7062	likely_pathogenic	0.7781	pathogenic	-0.225	Destabilizing	0.994	D	0.795	deleterious	N	0.503706635	None	None	N
E/W	0.9884	likely_pathogenic	0.9929	pathogenic	-0.434	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/Y	0.95	likely_pathogenic	0.9698	pathogenic	-0.342	Destabilizing	1.0	D	0.806	deleterious	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.