TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20654	62185;62186;62187	chr2:178589765;178589764;178589763	chr2:179454492;179454491;179454490
N2AB	19013	57262;57263;57264	chr2:178589765;178589764;178589763	chr2:179454492;179454491;179454490
N2A	18086	54481;54482;54483	chr2:178589765;178589764;178589763	chr2:179454492;179454491;179454490
N2B	11589	34990;34991;34992	chr2:178589765;178589764;178589763	chr2:179454492;179454491;179454490
Novex-1	11714	35365;35366;35367	chr2:178589765;178589764;178589763	chr2:179454492;179454491;179454490
Novex-2	11781	35566;35567;35568	chr2:178589765;178589764;178589763	chr2:179454492;179454491;179454490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-37
• Domain position: 86
• Structural Position: 121
• Q(SASA): 0.1278
• 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/T	rs1244996285	-2.003	0.016	N	0.361	0.093	0.33085137897	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs1244996285	-2.003	0.016	N	0.361	0.093	0.33085137897	gnomAD-4.0.0	1.59178E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43295E-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	0.1941	likely_benign	0.1842	benign	-1.657	Destabilizing	0.25	N	0.479	neutral	None	None	None	None	I
I/C	0.6324	likely_pathogenic	0.5946	pathogenic	-0.97	Destabilizing	0.977	D	0.54	neutral	None	None	None	None	I
I/D	0.7806	likely_pathogenic	0.6985	pathogenic	-0.938	Destabilizing	0.92	D	0.596	neutral	None	None	None	None	I
I/E	0.5532	ambiguous	0.4692	ambiguous	-0.932	Destabilizing	0.92	D	0.593	neutral	None	None	None	None	I
I/F	0.2779	likely_benign	0.2475	benign	-1.13	Destabilizing	0.81	D	0.552	neutral	N	0.453368531	None	None	I
I/G	0.6491	likely_pathogenic	0.609	pathogenic	-1.983	Destabilizing	0.766	D	0.591	neutral	None	None	None	None	I
I/H	0.6465	likely_pathogenic	0.5793	pathogenic	-1.166	Destabilizing	0.992	D	0.626	neutral	None	None	None	None	I
I/K	0.4351	ambiguous	0.3511	ambiguous	-1.068	Destabilizing	0.85	D	0.593	neutral	None	None	None	None	I
I/L	0.1442	likely_benign	0.1583	benign	-0.834	Destabilizing	0.099	N	0.443	neutral	N	0.348259863	None	None	I
I/M	0.1066	likely_benign	0.1034	benign	-0.662	Destabilizing	0.916	D	0.555	neutral	N	0.453541889	None	None	I
I/N	0.3226	likely_benign	0.2714	benign	-0.862	Destabilizing	0.896	D	0.595	neutral	N	0.453541889	None	None	I
I/P	0.9332	likely_pathogenic	0.9308	pathogenic	-1.077	Destabilizing	0.972	D	0.595	neutral	None	None	None	None	I
I/Q	0.4524	ambiguous	0.3808	ambiguous	-1.04	Destabilizing	0.972	D	0.625	neutral	None	None	None	None	I
I/R	0.3582	ambiguous	0.2861	benign	-0.498	Destabilizing	0.92	D	0.596	neutral	None	None	None	None	I
I/S	0.2606	likely_benign	0.2238	benign	-1.505	Destabilizing	0.379	N	0.531	neutral	N	0.441753523	None	None	I
I/T	0.1006	likely_benign	0.0879	benign	-1.385	Destabilizing	0.016	N	0.361	neutral	N	0.374387672	None	None	I
I/V	0.0621	likely_benign	0.0597	benign	-1.077	Destabilizing	0.001	N	0.214	neutral	N	0.374734389	None	None	I
I/W	0.9032	likely_pathogenic	0.8572	pathogenic	-1.179	Destabilizing	0.992	D	0.667	neutral	None	None	None	None	I
I/Y	0.6681	likely_pathogenic	0.6193	pathogenic	-0.961	Destabilizing	0.92	D	0.537	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.