TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27139	81640;81641;81642	chr2:178564717;178564716;178564715	chr2:179429444;179429443;179429442
N2AB	25498	76717;76718;76719	chr2:178564717;178564716;178564715	chr2:179429444;179429443;179429442
N2A	24571	73936;73937;73938	chr2:178564717;178564716;178564715	chr2:179429444;179429443;179429442
N2B	18074	54445;54446;54447	chr2:178564717;178564716;178564715	chr2:179429444;179429443;179429442
Novex-1	18199	54820;54821;54822	chr2:178564717;178564716;178564715	chr2:179429444;179429443;179429442
Novex-2	18266	55021;55022;55023	chr2:178564717;178564716;178564715	chr2:179429444;179429443;179429442
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: 68
• Structural Position: 99
• Q(SASA): 0.5176
• 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	rs763198311	-0.172	0.998	N	0.654	0.427	0.583897100485	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/K	rs763198311	-0.172	0.998	N	0.654	0.427	0.583897100485	gnomAD-4.0.0	2.05336E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31959E-05	1.65766E-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	0.3052	likely_benign	0.2396	benign	-0.516	Destabilizing	0.998	D	0.644	neutral	N	0.481115247	None	None	N
E/C	0.9467	likely_pathogenic	0.9262	pathogenic	-0.076	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/D	0.3685	ambiguous	0.3297	benign	-0.816	Destabilizing	0.434	N	0.204	neutral	N	0.506060039	None	None	N
E/F	0.96	likely_pathogenic	0.939	pathogenic	-0.542	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/G	0.5098	ambiguous	0.4435	ambiguous	-0.774	Destabilizing	0.999	D	0.622	neutral	N	0.509440627	None	None	N
E/H	0.8766	likely_pathogenic	0.8266	pathogenic	-0.751	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/I	0.6983	likely_pathogenic	0.6192	pathogenic	0.145	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/K	0.4693	ambiguous	0.3538	ambiguous	-0.19	Destabilizing	0.998	D	0.654	neutral	N	0.48792933	None	None	N
E/L	0.8183	likely_pathogenic	0.7412	pathogenic	0.145	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/M	0.8007	likely_pathogenic	0.7216	pathogenic	0.499	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
E/N	0.6619	likely_pathogenic	0.6044	pathogenic	-0.384	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.6927	likely_pathogenic	0.6056	pathogenic	-0.054	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/Q	0.3861	ambiguous	0.3013	benign	-0.349	Destabilizing	0.999	D	0.717	prob.delet.	N	0.485549474	None	None	N
E/R	0.6598	likely_pathogenic	0.551	ambiguous	-0.074	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/S	0.4767	ambiguous	0.3971	ambiguous	-0.602	Destabilizing	0.997	D	0.663	neutral	None	None	None	None	N
E/T	0.5399	ambiguous	0.4591	ambiguous	-0.409	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/V	0.4893	ambiguous	0.4075	ambiguous	-0.054	Destabilizing	1.0	D	0.669	neutral	N	0.517580928	None	None	N
E/W	0.9919	likely_pathogenic	0.9866	pathogenic	-0.469	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/Y	0.9393	likely_pathogenic	0.9073	pathogenic	-0.332	Destabilizing	1.0	D	0.677	prob.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.