TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9261	28006;28007;28008	chr2:178712049;178712048;178712047	chr2:179576776;179576775;179576774
N2AB	8944	27055;27056;27057	chr2:178712049;178712048;178712047	chr2:179576776;179576775;179576774
N2A	8017	24274;24275;24276	chr2:178712049;178712048;178712047	chr2:179576776;179576775;179576774
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-78
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2751
• 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
T/A	None	None	0.625	D	0.45	0.295	0.255777322467	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

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
T/A	0.0987	likely_benign	0.1293	benign	-1.004	Destabilizing	0.625	D	0.45	neutral	D	0.530099384	None	None	N
T/C	0.4178	ambiguous	0.5204	ambiguous	-0.731	Destabilizing	0.016	N	0.297	neutral	None	None	None	None	N
T/D	0.6166	likely_pathogenic	0.7083	pathogenic	-1.718	Destabilizing	0.974	D	0.538	neutral	None	None	None	None	N
T/E	0.4299	ambiguous	0.5296	ambiguous	-1.513	Destabilizing	0.842	D	0.503	neutral	None	None	None	None	N
T/F	0.2457	likely_benign	0.3531	ambiguous	-0.551	Destabilizing	0.991	D	0.637	neutral	None	None	None	None	N
T/G	0.4024	ambiguous	0.4934	ambiguous	-1.424	Destabilizing	0.915	D	0.557	neutral	None	None	None	None	N
T/H	0.3051	likely_benign	0.4095	ambiguous	-1.64	Destabilizing	0.993	D	0.62	neutral	None	None	None	None	N
T/I	0.1619	likely_benign	0.2269	benign	0.102	Stabilizing	0.966	D	0.535	neutral	D	0.530062098	None	None	N
T/K	0.3356	likely_benign	0.4339	ambiguous	-0.66	Destabilizing	0.669	D	0.501	neutral	D	0.536139922	None	None	N
T/L	0.118	likely_benign	0.1626	benign	0.102	Stabilizing	0.842	D	0.521	neutral	None	None	None	None	N
T/M	0.097	likely_benign	0.125	benign	0.035	Stabilizing	0.991	D	0.552	neutral	None	None	None	None	N
T/N	0.184	likely_benign	0.2418	benign	-1.372	Destabilizing	0.842	D	0.476	neutral	None	None	None	None	N
T/P	0.83	likely_pathogenic	0.9028	pathogenic	-0.235	Destabilizing	0.989	D	0.549	neutral	N	0.519377441	None	None	N
T/Q	0.3015	likely_benign	0.3938	ambiguous	-1.077	Destabilizing	0.949	D	0.549	neutral	None	None	None	None	N
T/R	0.25	likely_benign	0.3576	ambiguous	-0.947	Destabilizing	0.012	N	0.285	neutral	N	0.469685643	None	None	N
T/S	0.1209	likely_benign	0.1412	benign	-1.495	Destabilizing	0.801	D	0.494	neutral	N	0.457620423	None	None	N
T/V	0.1303	likely_benign	0.168	benign	-0.235	Destabilizing	0.842	D	0.453	neutral	None	None	None	None	N
T/W	0.6532	likely_pathogenic	0.7711	pathogenic	-0.844	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
T/Y	0.2995	likely_benign	0.4073	ambiguous	-0.436	Destabilizing	0.991	D	0.637	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.