TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27955	84088;84089;84090	chr2:178562269;178562268;178562267	chr2:179426996;179426995;179426994
N2AB	26314	79165;79166;79167	chr2:178562269;178562268;178562267	chr2:179426996;179426995;179426994
N2A	25387	76384;76385;76386	chr2:178562269;178562268;178562267	chr2:179426996;179426995;179426994
N2B	18890	56893;56894;56895	chr2:178562269;178562268;178562267	chr2:179426996;179426995;179426994
Novex-1	19015	57268;57269;57270	chr2:178562269;178562268;178562267	chr2:179426996;179426995;179426994
Novex-2	19082	57469;57470;57471	chr2:178562269;178562268;178562267	chr2:179426996;179426995;179426994
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-91
• Domain position: 93
• Structural Position: 129
• Q(SASA): 0.5067
• 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
I/N	None	None	0.877	N	0.533	0.309	0.732347765206	gnomAD-4.0.0	1.59219E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43398E-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
I/A	0.2449	likely_benign	0.2427	benign	-1.297	Destabilizing	0.083	N	0.416	neutral	None	None	None	None	I
I/C	0.7292	likely_pathogenic	0.7322	pathogenic	-0.855	Destabilizing	0.922	D	0.384	neutral	None	None	None	None	I
I/D	0.8005	likely_pathogenic	0.8281	pathogenic	-0.602	Destabilizing	0.757	D	0.581	neutral	None	None	None	None	I
I/E	0.5866	likely_pathogenic	0.6247	pathogenic	-0.613	Destabilizing	0.697	D	0.523	neutral	None	None	None	None	I
I/F	0.1807	likely_benign	0.2072	benign	-0.826	Destabilizing	0.316	N	0.384	neutral	N	0.519471384	None	None	I
I/G	0.705	likely_pathogenic	0.717	pathogenic	-1.587	Destabilizing	0.757	D	0.494	neutral	None	None	None	None	I
I/H	0.5452	ambiguous	0.5689	pathogenic	-0.704	Destabilizing	0.937	D	0.551	neutral	None	None	None	None	I
I/K	0.3799	ambiguous	0.4161	ambiguous	-0.887	Destabilizing	0.084	N	0.529	neutral	None	None	None	None	I
I/L	0.1249	likely_benign	0.1197	benign	-0.593	Destabilizing	None	N	0.109	neutral	N	0.472810801	None	None	I
I/M	0.0998	likely_benign	0.1027	benign	-0.547	Destabilizing	0.122	N	0.478	neutral	D	0.530245738	None	None	I
I/N	0.3661	ambiguous	0.3885	ambiguous	-0.743	Destabilizing	0.877	D	0.533	neutral	N	0.481409915	None	None	I
I/P	0.7762	likely_pathogenic	0.7823	pathogenic	-0.795	Destabilizing	0.905	D	0.583	neutral	None	None	None	None	I
I/Q	0.412	ambiguous	0.4322	ambiguous	-0.907	Destabilizing	0.797	D	0.521	neutral	None	None	None	None	I
I/R	0.2917	likely_benign	0.3289	benign	-0.296	Destabilizing	0.554	D	0.541	neutral	None	None	None	None	I
I/S	0.2826	likely_benign	0.2893	benign	-1.334	Destabilizing	0.537	D	0.457	neutral	N	0.486636927	None	None	I
I/T	0.0999	likely_benign	0.0998	benign	-1.229	Destabilizing	0.09	N	0.385	neutral	N	0.432081686	None	None	I
I/V	0.068	likely_benign	0.062	benign	-0.795	Destabilizing	None	N	0.074	neutral	N	0.418034954	None	None	I
I/W	0.8012	likely_pathogenic	0.8392	pathogenic	-0.87	Destabilizing	0.982	D	0.637	neutral	None	None	None	None	I
I/Y	0.5627	ambiguous	0.591	pathogenic	-0.652	Destabilizing	0.127	N	0.457	neutral	None	None	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.