TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8934	27025;27026;27027	chr2:178713334;178713333;178713332	chr2:179578061;179578060;179578059
N2AB	8617	26074;26075;26076	chr2:178713334;178713333;178713332	chr2:179578061;179578060;179578059
N2A	7690	23293;23294;23295	chr2:178713334;178713333;178713332	chr2:179578061;179578060;179578059
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-75
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.474
• 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	rs2076941615	None	0.822	N	0.471	0.208	0.227260227426	gnomAD-4.0.0	1.7432E-06	None	None	None	None	N	None	0	2.8082E-05	None	0	0	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	0.0958	likely_benign	0.0966	benign	-0.394	Destabilizing	0.822	D	0.437	neutral	N	0.462769087	None	None	N
E/C	0.7445	likely_pathogenic	0.7525	pathogenic	0.001	Stabilizing	0.998	D	0.656	neutral	None	None	None	None	N
E/D	0.0935	likely_benign	0.0956	benign	-0.415	Destabilizing	0.006	N	0.071	neutral	N	0.350576945	None	None	N
E/F	0.5831	likely_pathogenic	0.623	pathogenic	-0.36	Destabilizing	0.993	D	0.571	neutral	None	None	None	None	N
E/G	0.0885	likely_benign	0.0922	benign	-0.595	Destabilizing	0.822	D	0.434	neutral	N	0.448685069	None	None	N
E/H	0.3468	ambiguous	0.3678	ambiguous	-0.229	Destabilizing	0.978	D	0.439	neutral	None	None	None	None	N
E/I	0.2589	likely_benign	0.2895	benign	0.102	Stabilizing	0.978	D	0.559	neutral	None	None	None	None	N
E/K	0.0992	likely_benign	0.1119	benign	0.221	Stabilizing	0.822	D	0.471	neutral	N	0.456669834	None	None	N
E/L	0.2848	likely_benign	0.3138	benign	0.102	Stabilizing	0.978	D	0.481	neutral	None	None	None	None	N
E/M	0.3246	likely_benign	0.3478	ambiguous	0.246	Stabilizing	0.998	D	0.542	neutral	None	None	None	None	N
E/N	0.1563	likely_benign	0.1708	benign	-0.001	Destabilizing	0.076	N	0.208	neutral	None	None	None	None	N
E/P	0.2551	likely_benign	0.2469	benign	-0.043	Destabilizing	0.978	D	0.463	neutral	None	None	None	None	N
E/Q	0.1123	likely_benign	0.117	benign	0.02	Stabilizing	0.904	D	0.457	neutral	N	0.459075421	None	None	N
E/R	0.1708	likely_benign	0.1866	benign	0.393	Stabilizing	0.978	D	0.437	neutral	None	None	None	None	N
E/S	0.1415	likely_benign	0.1532	benign	-0.178	Destabilizing	0.86	D	0.43	neutral	None	None	None	None	N
E/T	0.1579	likely_benign	0.1714	benign	-0.022	Destabilizing	0.86	D	0.446	neutral	None	None	None	None	N
E/V	0.1417	likely_benign	0.1531	benign	-0.043	Destabilizing	0.97	D	0.455	neutral	N	0.477487823	None	None	N
E/W	0.7568	likely_pathogenic	0.7862	pathogenic	-0.241	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
E/Y	0.4172	ambiguous	0.4437	ambiguous	-0.127	Destabilizing	0.993	D	0.556	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.