TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33775	101548;101549;101550	chr2:178535292;178535291;178535290	chr2:179400019;179400018;179400017
N2AB	32134	96625;96626;96627	chr2:178535292;178535291;178535290	chr2:179400019;179400018;179400017
N2A	31207	93844;93845;93846	chr2:178535292;178535291;178535290	chr2:179400019;179400018;179400017
N2B	24710	74353;74354;74355	chr2:178535292;178535291;178535290	chr2:179400019;179400018;179400017
Novex-1	24835	74728;74729;74730	chr2:178535292;178535291;178535290	chr2:179400019;179400018;179400017
Novex-2	24902	74929;74930;74931	chr2:178535292;178535291;178535290	chr2:179400019;179400018;179400017
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: Fn3-132
• Domain position: 87
• Structural Position: 122
• Q(SASA): 0.7053
• 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/G	None	None	0.379	D	0.598	0.207	0.414670632993	gnomAD-4.0.0	1.59109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85786E-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	0.1447	likely_benign	0.1798	benign	-0.162	Destabilizing	0.084	N	0.582	neutral	N	0.499669328	None	None	N
E/C	0.8718	likely_pathogenic	0.8947	pathogenic	-0.122	Destabilizing	0.952	D	0.806	deleterious	None	None	None	None	N
E/D	0.1167	likely_benign	0.1393	benign	-0.284	Destabilizing	None	N	0.28	neutral	N	0.498437177	None	None	N
E/F	0.7286	likely_pathogenic	0.7932	pathogenic	-0.061	Destabilizing	0.907	D	0.742	deleterious	None	None	None	None	N
E/G	0.2132	likely_benign	0.2518	benign	-0.314	Destabilizing	0.379	N	0.598	neutral	D	0.527568006	None	None	N
E/H	0.5615	ambiguous	0.6311	pathogenic	0.434	Stabilizing	0.696	D	0.694	prob.delet.	None	None	None	None	N
E/I	0.2923	likely_benign	0.3695	ambiguous	0.188	Stabilizing	0.6	D	0.751	deleterious	None	None	None	None	N
E/K	0.182	likely_benign	0.2045	benign	0.478	Stabilizing	0.145	N	0.611	neutral	N	0.511425117	None	None	N
E/L	0.317	likely_benign	0.3883	ambiguous	0.188	Stabilizing	0.425	N	0.595	neutral	None	None	None	None	N
E/M	0.4226	ambiguous	0.4984	ambiguous	0.082	Stabilizing	0.503	D	0.761	deleterious	None	None	None	None	N
E/N	0.2507	likely_benign	0.3365	benign	0.08	Stabilizing	0.256	N	0.611	neutral	None	None	None	None	N
E/P	0.4017	ambiguous	0.4809	ambiguous	0.09	Stabilizing	None	N	0.39	neutral	None	None	None	None	N
E/Q	0.1715	likely_benign	0.1925	benign	0.121	Stabilizing	0.007	N	0.3	neutral	N	0.483585155	None	None	N
E/R	0.3564	ambiguous	0.3832	ambiguous	0.704	Stabilizing	0.441	N	0.644	neutral	None	None	None	None	N
E/S	0.1954	likely_benign	0.2561	benign	-0.031	Destabilizing	0.108	N	0.527	neutral	None	None	None	None	N
E/T	0.2108	likely_benign	0.279	benign	0.105	Stabilizing	0.251	N	0.632	neutral	None	None	None	None	N
E/V	0.1808	likely_benign	0.223	benign	0.09	Stabilizing	0.284	N	0.583	neutral	N	0.518775164	None	None	N
E/W	0.9346	likely_pathogenic	0.947	pathogenic	0.053	Stabilizing	0.99	D	0.811	deleterious	None	None	None	None	N
E/Y	0.648	likely_pathogenic	0.7149	pathogenic	0.178	Stabilizing	0.895	D	0.77	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.