TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17828	53707;53708;53709	chr2:178607120;178607119;178607118	chr2:179471847;179471846;179471845
N2AB	16187	48784;48785;48786	chr2:178607120;178607119;178607118	chr2:179471847;179471846;179471845
N2A	15260	46003;46004;46005	chr2:178607120;178607119;178607118	chr2:179471847;179471846;179471845
N2B	8763	26512;26513;26514	chr2:178607120;178607119;178607118	chr2:179471847;179471846;179471845
Novex-1	8888	26887;26888;26889	chr2:178607120;178607119;178607118	chr2:179471847;179471846;179471845
Novex-2	8955	27088;27089;27090	chr2:178607120;178607119;178607118	chr2:179471847;179471846;179471845
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-17
• Domain position: 65
• Structural Position: 98
• Q(SASA): 0.6346
• 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
L/V	None	None	None	N	0.12	0.044	0.0986583533028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
L/A	0.5258	ambiguous	0.4185	ambiguous	-1.228	Destabilizing	0.035	N	0.352	neutral	None	None	None	None	N
L/C	0.8031	likely_pathogenic	0.7322	pathogenic	-0.82	Destabilizing	0.935	D	0.371	neutral	None	None	None	None	N
L/D	0.9518	likely_pathogenic	0.9238	pathogenic	-0.24	Destabilizing	0.555	D	0.461	neutral	None	None	None	None	N
L/E	0.7986	likely_pathogenic	0.7075	pathogenic	-0.246	Destabilizing	0.555	D	0.457	neutral	None	None	None	None	N
L/F	0.4617	ambiguous	0.3899	ambiguous	-0.789	Destabilizing	0.317	N	0.323	neutral	N	0.481848785	None	None	N
L/G	0.8505	likely_pathogenic	0.7796	pathogenic	-1.514	Destabilizing	0.555	D	0.449	neutral	None	None	None	None	N
L/H	0.7045	likely_pathogenic	0.6152	pathogenic	-0.546	Destabilizing	0.915	D	0.465	neutral	N	0.49739424	None	None	N
L/I	0.1258	likely_benign	0.0907	benign	-0.538	Destabilizing	None	N	0.087	neutral	N	0.406446949	None	None	N
L/K	0.678	likely_pathogenic	0.6116	pathogenic	-0.663	Destabilizing	0.555	D	0.439	neutral	None	None	None	None	N
L/M	0.1718	likely_benign	0.1296	benign	-0.521	Destabilizing	0.007	N	0.267	neutral	None	None	None	None	N
L/N	0.6923	likely_pathogenic	0.5692	pathogenic	-0.546	Destabilizing	0.791	D	0.455	neutral	None	None	None	None	N
L/P	0.8817	likely_pathogenic	0.8533	pathogenic	-0.735	Destabilizing	0.741	D	0.457	neutral	N	0.503320135	None	None	N
L/Q	0.4137	ambiguous	0.3427	ambiguous	-0.685	Destabilizing	0.555	D	0.439	neutral	None	None	None	None	N
L/R	0.6336	likely_pathogenic	0.5654	pathogenic	-0.109	Destabilizing	0.484	N	0.445	neutral	N	0.471359645	None	None	N
L/S	0.6719	likely_pathogenic	0.5736	pathogenic	-1.198	Destabilizing	0.555	D	0.41	neutral	None	None	None	None	N
L/T	0.4366	ambiguous	0.3328	benign	-1.079	Destabilizing	0.149	N	0.39	neutral	None	None	None	None	N
L/V	0.1406	likely_benign	0.1043	benign	-0.735	Destabilizing	None	N	0.12	neutral	N	0.396056597	None	None	N
L/W	0.7167	likely_pathogenic	0.6735	pathogenic	-0.809	Destabilizing	0.935	D	0.521	neutral	None	None	None	None	N
L/Y	0.7661	likely_pathogenic	0.7002	pathogenic	-0.581	Destabilizing	0.555	D	0.358	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.