TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24900	74923;74924;74925	chr2:178571434;178571433;178571432	chr2:179436161;179436160;179436159
N2AB	23259	70000;70001;70002	chr2:178571434;178571433;178571432	chr2:179436161;179436160;179436159
N2A	22332	67219;67220;67221	chr2:178571434;178571433;178571432	chr2:179436161;179436160;179436159
N2B	15835	47728;47729;47730	chr2:178571434;178571433;178571432	chr2:179436161;179436160;179436159
Novex-1	15960	48103;48104;48105	chr2:178571434;178571433;178571432	chr2:179436161;179436160;179436159
Novex-2	16027	48304;48305;48306	chr2:178571434;178571433;178571432	chr2:179436161;179436160;179436159
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-68
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.3625
• 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	0.001	N	0.201	0.116	0.0297737177859	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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	0.0705	likely_benign	0.0716	benign	-0.769	Destabilizing	0.001	N	0.201	neutral	N	0.428587516	None	None	N
T/C	0.1972	likely_benign	0.2028	benign	-0.567	Destabilizing	0.204	N	0.315	neutral	None	None	None	None	N
T/D	0.5269	ambiguous	0.538	ambiguous	-0.469	Destabilizing	0.068	N	0.456	neutral	None	None	None	None	N
T/E	0.2596	likely_benign	0.2657	benign	-0.363	Destabilizing	0.068	N	0.371	neutral	None	None	None	None	N
T/F	0.1336	likely_benign	0.1462	benign	-0.592	Destabilizing	0.035	N	0.543	neutral	None	None	None	None	N
T/G	0.2928	likely_benign	0.2967	benign	-1.119	Destabilizing	0.029	N	0.355	neutral	None	None	None	None	N
T/H	0.2414	likely_benign	0.2426	benign	-1.216	Destabilizing	0.439	N	0.484	neutral	None	None	None	None	N
T/I	0.0434	likely_benign	0.0462	benign	0.105	Stabilizing	None	N	0.098	neutral	N	0.307874678	None	None	N
T/K	0.179	likely_benign	0.1763	benign	-0.655	Destabilizing	0.068	N	0.369	neutral	None	None	None	None	N
T/L	0.0542	likely_benign	0.0567	benign	0.105	Stabilizing	None	N	0.159	neutral	None	None	None	None	N
T/M	0.0551	likely_benign	0.0587	benign	0.06	Stabilizing	0.035	N	0.507	neutral	None	None	None	None	N
T/N	0.1996	likely_benign	0.2149	benign	-0.968	Destabilizing	0.144	N	0.343	neutral	N	0.473341158	None	None	N
T/P	0.6443	likely_pathogenic	0.6665	pathogenic	-0.153	Destabilizing	0.052	N	0.459	neutral	N	0.473341158	None	None	N
T/Q	0.1951	likely_benign	0.1929	benign	-0.861	Destabilizing	0.439	N	0.493	neutral	None	None	None	None	N
T/R	0.1481	likely_benign	0.1381	benign	-0.627	Destabilizing	0.068	N	0.477	neutral	None	None	None	None	N
T/S	0.1289	likely_benign	0.1328	benign	-1.233	Destabilizing	0.011	N	0.185	neutral	N	0.471260858	None	None	N
T/V	0.0395	likely_benign	0.0409	benign	-0.153	Destabilizing	None	N	0.07	neutral	None	None	None	None	N
T/W	0.5262	ambiguous	0.5528	ambiguous	-0.677	Destabilizing	0.747	D	0.508	neutral	None	None	None	None	N
T/Y	0.224	likely_benign	0.2381	benign	-0.36	Destabilizing	0.068	N	0.597	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.