TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13966	42121;42122;42123	chr2:178635293;178635292;178635291	chr2:179500020;179500019;179500018
N2AB	12325	37198;37199;37200	chr2:178635293;178635292;178635291	chr2:179500020;179500019;179500018
N2A	11398	34417;34418;34419	chr2:178635293;178635292;178635291	chr2:179500020;179500019;179500018
N2B	4901	14926;14927;14928	chr2:178635293;178635292;178635291	chr2:179500020;179500019;179500018
Novex-1	5026	15301;15302;15303	chr2:178635293;178635292;178635291	chr2:179500020;179500019;179500018
Novex-2	5093	15502;15503;15504	chr2:178635293;178635292;178635291	chr2:179500020;179500019;179500018
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-90
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.775
• 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/Q	None	None	0.001	N	0.279	0.095	0.168933306366	gnomAD-4.0.0	1.59281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86049E-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	0.2559	likely_benign	0.2164	benign	-0.392	Destabilizing	0.061	N	0.551	neutral	D	0.548867108	None	None	N
E/C	0.9173	likely_pathogenic	0.9131	pathogenic	-0.236	Destabilizing	0.934	D	0.854	deleterious	None	None	None	None	N
E/D	0.192	likely_benign	0.1276	benign	-0.422	Destabilizing	None	N	0.233	neutral	N	0.483335599	None	None	N
E/F	0.8652	likely_pathogenic	0.8345	pathogenic	-0.064	Destabilizing	0.789	D	0.78	deleterious	None	None	None	None	N
E/G	0.454	ambiguous	0.3447	ambiguous	-0.616	Destabilizing	0.115	N	0.593	neutral	D	0.551394562	None	None	N
E/H	0.6826	likely_pathogenic	0.6	pathogenic	0.266	Stabilizing	0.378	N	0.583	neutral	None	None	None	None	N
E/I	0.4903	ambiguous	0.4596	ambiguous	0.174	Stabilizing	0.552	D	0.821	deleterious	None	None	None	None	N
E/K	0.3828	ambiguous	0.3082	benign	0.271	Stabilizing	0.002	N	0.313	neutral	N	0.493779559	None	None	N
E/L	0.5499	ambiguous	0.5056	ambiguous	0.174	Stabilizing	0.378	N	0.578	neutral	None	None	None	None	N
E/M	0.5793	likely_pathogenic	0.579	pathogenic	0.15	Stabilizing	0.823	D	0.784	deleterious	None	None	None	None	N
E/N	0.3598	ambiguous	0.2789	benign	-0.247	Destabilizing	0.08	N	0.576	neutral	None	None	None	None	N
E/P	0.875	likely_pathogenic	0.8003	pathogenic	0.006	Stabilizing	0.552	D	0.639	neutral	None	None	None	None	N
E/Q	0.1649	likely_benign	0.1776	benign	-0.177	Destabilizing	0.001	N	0.279	neutral	N	0.506878524	None	None	N
E/R	0.5376	ambiguous	0.4587	ambiguous	0.584	Stabilizing	0.08	N	0.576	neutral	None	None	None	None	N
E/S	0.2981	likely_benign	0.2386	benign	-0.384	Destabilizing	0.08	N	0.46	neutral	None	None	None	None	N
E/T	0.283	likely_benign	0.2375	benign	-0.192	Destabilizing	0.378	N	0.587	neutral	None	None	None	None	N
E/V	0.3143	likely_benign	0.28	benign	0.006	Stabilizing	0.314	N	0.603	neutral	N	0.505657197	None	None	N
E/W	0.9624	likely_pathogenic	0.9536	pathogenic	0.145	Stabilizing	0.934	D	0.866	deleterious	None	None	None	None	N
E/Y	0.8098	likely_pathogenic	0.7501	pathogenic	0.193	Stabilizing	0.552	D	0.811	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.