TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20034	60325;60326;60327	chr2:178591719;178591718;178591717	chr2:179456446;179456445;179456444
N2AB	18393	55402;55403;55404	chr2:178591719;178591718;178591717	chr2:179456446;179456445;179456444
N2A	17466	52621;52622;52623	chr2:178591719;178591718;178591717	chr2:179456446;179456445;179456444
N2B	10969	33130;33131;33132	chr2:178591719;178591718;178591717	chr2:179456446;179456445;179456444
Novex-1	11094	33505;33506;33507	chr2:178591719;178591718;178591717	chr2:179456446;179456445;179456444
Novex-2	11161	33706;33707;33708	chr2:178591719;178591718;178591717	chr2:179456446;179456445;179456444
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: Fn3-33
• Domain position: 58
• Structural Position: 90
• Q(SASA): 0.4955
• 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	None	None	None	N	0.201	0.058	0.117506650769	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	0	None	0	0	1.3125E-06	0	0
E/G	None	None	0.124	N	0.555	0.112	0.223146558224	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
E/Q	rs746056036	-0.624	0.497	N	0.566	0.159	0.234412748748	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	0	None	0	4.47377E-04	None	0	None	0	0	0
E/Q	rs746056036	-0.624	0.497	N	0.566	0.159	0.234412748748	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94553E-04	None	0	0	0	0	0
E/Q	rs746056036	-0.624	0.497	N	0.566	0.159	0.234412748748	gnomAD-4.0.0	5.57843E-06	None	None	None	None	N	None	0	0	None	0	2.01117E-04	None	0	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	0.1402	likely_benign	0.136	benign	-0.571	Destabilizing	0.001	N	0.378	neutral	N	0.487003889	None	None	N
E/C	0.7437	likely_pathogenic	0.7456	pathogenic	-0.401	Destabilizing	0.909	D	0.709	prob.delet.	None	None	None	None	N
E/D	0.1312	likely_benign	0.1082	benign	-0.833	Destabilizing	None	N	0.201	neutral	N	0.505552364	None	None	N
E/F	0.6721	likely_pathogenic	0.6493	pathogenic	0.23	Stabilizing	0.726	D	0.691	prob.neutral	None	None	None	None	N
E/G	0.1899	likely_benign	0.1917	benign	-0.939	Destabilizing	0.124	N	0.555	neutral	N	0.507360518	None	None	N
E/H	0.2968	likely_benign	0.2981	benign	0.206	Stabilizing	0.567	D	0.598	neutral	None	None	None	None	N
E/I	0.3881	ambiguous	0.38	ambiguous	0.431	Stabilizing	0.567	D	0.677	prob.neutral	None	None	None	None	N
E/K	0.1924	likely_benign	0.2168	benign	-0.305	Destabilizing	0.124	N	0.505	neutral	N	0.469572921	None	None	N
E/L	0.4352	ambiguous	0.4224	ambiguous	0.431	Stabilizing	0.396	N	0.61	neutral	None	None	None	None	N
E/M	0.4681	ambiguous	0.4435	ambiguous	0.621	Stabilizing	0.909	D	0.661	neutral	None	None	None	None	N
E/N	0.1886	likely_benign	0.1593	benign	-0.944	Destabilizing	0.003	N	0.385	neutral	None	None	None	None	N
E/P	0.8954	likely_pathogenic	0.8964	pathogenic	0.119	Stabilizing	0.567	D	0.626	neutral	None	None	None	None	N
E/Q	0.1119	likely_benign	0.1169	benign	-0.776	Destabilizing	0.497	N	0.566	neutral	N	0.455758262	None	None	N
E/R	0.2655	likely_benign	0.2876	benign	0.101	Stabilizing	0.567	D	0.572	neutral	None	None	None	None	N
E/S	0.1408	likely_benign	0.1309	benign	-1.215	Destabilizing	0.157	N	0.495	neutral	None	None	None	None	N
E/T	0.1764	likely_benign	0.1688	benign	-0.899	Destabilizing	0.157	N	0.543	neutral	None	None	None	None	N
E/V	0.2352	likely_benign	0.2276	benign	0.119	Stabilizing	0.331	N	0.582	neutral	N	0.476557608	None	None	N
E/W	0.845	likely_pathogenic	0.8372	pathogenic	0.529	Stabilizing	0.968	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.5006	ambiguous	0.492	ambiguous	0.506	Stabilizing	0.726	D	0.669	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.