TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4715	14368;14369;14370	chr2:178738310;178738309;178738308	chr2:179603037;179603036;179603035
N2AB	4398	13417;13418;13419	chr2:178738310;178738309;178738308	chr2:179603037;179603036;179603035
N2A	3471	10636;10637;10638	chr2:178738310;178738309;178738308	chr2:179603037;179603036;179603035
N2B	4352	13279;13280;13281	chr2:178738310;178738309;178738308	chr2:179603037;179603036;179603035
Novex-1	4477	13654;13655;13656	chr2:178738310;178738309;178738308	chr2:179603037;179603036;179603035
Novex-2	4544	13855;13856;13857	chr2:178738310;178738309;178738308	chr2:179603037;179603036;179603035
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-30
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.7508
• Predicted PPI site: I

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
H/Y	rs376855980	0.984	0.969	N	0.295	0.179	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
H/A	0.7855	likely_pathogenic	0.7761	pathogenic	0.114	Stabilizing	0.38	N	0.255	neutral	None	None	None	None	I
H/C	0.5872	likely_pathogenic	0.5289	ambiguous	0.504	Stabilizing	0.998	D	0.293	neutral	None	None	None	None	I
H/D	0.6461	likely_pathogenic	0.5935	pathogenic	0.058	Stabilizing	0.007	N	0.148	neutral	N	0.420218994	None	None	I
H/E	0.7389	likely_pathogenic	0.7352	pathogenic	0.072	Stabilizing	0.584	D	0.213	neutral	None	None	None	None	I
H/F	0.5898	likely_pathogenic	0.6033	pathogenic	0.673	Stabilizing	0.993	D	0.347	neutral	None	None	None	None	I
H/G	0.7608	likely_pathogenic	0.7386	pathogenic	-0.147	Destabilizing	0.009	N	0.127	neutral	None	None	None	None	I
H/I	0.8018	likely_pathogenic	0.8052	pathogenic	0.77	Stabilizing	0.98	D	0.381	neutral	None	None	None	None	I
H/K	0.7323	likely_pathogenic	0.7003	pathogenic	0.058	Stabilizing	0.737	D	0.299	neutral	None	None	None	None	I
H/L	0.4225	ambiguous	0.4155	ambiguous	0.77	Stabilizing	0.912	D	0.393	neutral	N	0.441145034	None	None	I
H/M	0.833	likely_pathogenic	0.8332	pathogenic	0.604	Stabilizing	0.993	D	0.3	neutral	None	None	None	None	I
H/N	0.2694	likely_benign	0.2591	benign	0.102	Stabilizing	0.028	N	0.129	neutral	N	0.405219223	None	None	I
H/P	0.7984	likely_pathogenic	0.8365	pathogenic	0.577	Stabilizing	0.912	D	0.38	neutral	N	0.430341751	None	None	I
H/Q	0.5426	ambiguous	0.5526	ambiguous	0.172	Stabilizing	0.912	D	0.259	neutral	N	0.387291005	None	None	I
H/R	0.443	ambiguous	0.4153	ambiguous	-0.381	Destabilizing	0.912	D	0.215	neutral	N	0.433598168	None	None	I
H/S	0.5953	likely_pathogenic	0.5754	pathogenic	0.108	Stabilizing	0.1	N	0.131	neutral	None	None	None	None	I
H/T	0.7757	likely_pathogenic	0.7566	pathogenic	0.218	Stabilizing	0.584	D	0.309	neutral	None	None	None	None	I
H/V	0.7478	likely_pathogenic	0.7518	pathogenic	0.577	Stabilizing	0.932	D	0.376	neutral	None	None	None	None	I
H/W	0.7735	likely_pathogenic	0.7609	pathogenic	0.677	Stabilizing	0.998	D	0.299	neutral	None	None	None	None	I
H/Y	0.2345	likely_benign	0.2188	benign	0.97	Stabilizing	0.969	D	0.295	neutral	N	0.446682385	None	None	I

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.