TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27142	81649;81650;81651	chr2:178564708;178564707;178564706	chr2:179429435;179429434;179429433
N2AB	25501	76726;76727;76728	chr2:178564708;178564707;178564706	chr2:179429435;179429434;179429433
N2A	24574	73945;73946;73947	chr2:178564708;178564707;178564706	chr2:179429435;179429434;179429433
N2B	18077	54454;54455;54456	chr2:178564708;178564707;178564706	chr2:179429435;179429434;179429433
Novex-1	18202	54829;54830;54831	chr2:178564708;178564707;178564706	chr2:179429435;179429434;179429433
Novex-2	18269	55030;55031;55032	chr2:178564708;178564707;178564706	chr2:179429435;179429434;179429433
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-85
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3509
• 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/K	None	None	0.822	N	0.493	0.247	0.29278752	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.2093	likely_benign	0.1721	benign	-1.003	Destabilizing	0.698	D	0.545	neutral	N	0.48327175	None	None	N
E/C	0.8894	likely_pathogenic	0.856	pathogenic	-0.656	Destabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
E/D	0.5108	ambiguous	0.4825	ambiguous	-1.449	Destabilizing	0.822	D	0.461	neutral	N	0.47667515	None	None	N
E/F	0.892	likely_pathogenic	0.8602	pathogenic	-0.493	Destabilizing	0.956	D	0.799	deleterious	None	None	None	None	N
E/G	0.358	ambiguous	0.2966	benign	-1.429	Destabilizing	0.822	D	0.661	neutral	N	0.49538854	None	None	N
E/H	0.8345	likely_pathogenic	0.795	pathogenic	-0.898	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
E/I	0.5453	ambiguous	0.4712	ambiguous	0.187	Stabilizing	0.915	D	0.753	deleterious	None	None	None	None	N
E/K	0.5613	ambiguous	0.5139	ambiguous	-1.261	Destabilizing	0.822	D	0.493	neutral	N	0.47581255	None	None	N
E/L	0.59	likely_pathogenic	0.5235	ambiguous	0.187	Stabilizing	0.514	D	0.619	neutral	None	None	None	None	N
E/M	0.5834	likely_pathogenic	0.5104	ambiguous	0.822	Stabilizing	0.559	D	0.48	neutral	None	None	None	None	N
E/N	0.6776	likely_pathogenic	0.6315	pathogenic	-1.635	Destabilizing	0.956	D	0.594	neutral	None	None	None	None	N
E/P	0.7723	likely_pathogenic	0.7371	pathogenic	-0.189	Destabilizing	0.978	D	0.737	prob.delet.	None	None	None	None	N
E/Q	0.2372	likely_benign	0.21	benign	-1.397	Destabilizing	0.97	D	0.585	neutral	N	0.51696146	None	None	N
E/R	0.6747	likely_pathogenic	0.6256	pathogenic	-1.05	Destabilizing	0.956	D	0.598	neutral	None	None	None	None	N
E/S	0.3676	ambiguous	0.3161	benign	-2.118	Highly Destabilizing	0.754	D	0.479	neutral	None	None	None	None	N
E/T	0.422	ambiguous	0.3621	ambiguous	-1.756	Destabilizing	0.019	N	0.327	neutral	None	None	None	None	N
E/V	0.3624	ambiguous	0.3005	benign	-0.189	Destabilizing	0.698	D	0.636	neutral	N	0.47967735	None	None	N
E/W	0.974	likely_pathogenic	0.9644	pathogenic	-0.409	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
E/Y	0.8527	likely_pathogenic	0.8162	pathogenic	-0.297	Destabilizing	0.978	D	0.789	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.