TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2492	7699;7700;7701	chr2:178773582;178773581;178773580	chr2:179638309;179638308;179638307
N2AB	2492	7699;7700;7701	chr2:178773582;178773581;178773580	chr2:179638309;179638308;179638307
N2A	2492	7699;7700;7701	chr2:178773582;178773581;178773580	chr2:179638309;179638308;179638307
N2B	2446	7561;7562;7563	chr2:178773582;178773581;178773580	chr2:179638309;179638308;179638307
Novex-1	2446	7561;7562;7563	chr2:178773582;178773581;178773580	chr2:179638309;179638308;179638307
Novex-2	2446	7561;7562;7563	chr2:178773582;178773581;178773580	chr2:179638309;179638308;179638307
Novex-3	2492	7699;7700;7701	chr2:178773582;178773581;178773580	chr2:179638309;179638308;179638307

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-14
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3589
• 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
Q/P	None	None	0.484	D	0.414	0.48	0.452546404249	gnomAD-4.0.0	1.59067E-06	None	None	None	None	N	None	5.65355E-05	0	None	0	0	None	0	0	0	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
Q/A	0.2562	likely_benign	0.2685	benign	-0.531	Destabilizing	0.149	N	0.366	neutral	None	None	None	None	N
Q/C	0.6213	likely_pathogenic	0.6415	pathogenic	-0.07	Destabilizing	0.935	D	0.594	neutral	None	None	None	None	N
Q/D	0.4654	ambiguous	0.498	ambiguous	-1.149	Destabilizing	0.149	N	0.296	neutral	None	None	None	None	N
Q/E	0.1052	likely_benign	0.108	benign	-1.032	Destabilizing	0.027	N	0.351	neutral	N	0.502715164	None	None	N
Q/F	0.6698	likely_pathogenic	0.6816	pathogenic	-0.241	Destabilizing	0.38	N	0.567	neutral	None	None	None	None	N
Q/G	0.3978	ambiguous	0.4212	ambiguous	-0.908	Destabilizing	0.149	N	0.431	neutral	None	None	None	None	N
Q/H	0.1911	likely_benign	0.2015	benign	-0.925	Destabilizing	0.001	N	0.19	neutral	N	0.509529601	None	None	N
Q/I	0.3818	ambiguous	0.3941	ambiguous	0.438	Stabilizing	0.555	D	0.562	neutral	None	None	None	None	N
Q/K	0.1297	likely_benign	0.1363	benign	-0.481	Destabilizing	0.002	N	0.167	neutral	N	0.498904921	None	None	N
Q/L	0.1563	likely_benign	0.1593	benign	0.438	Stabilizing	0.117	N	0.457	neutral	D	0.54055012	None	None	N
Q/M	0.3621	ambiguous	0.3631	ambiguous	0.902	Stabilizing	0.791	D	0.411	neutral	None	None	None	None	N
Q/N	0.282	likely_benign	0.2913	benign	-1.106	Destabilizing	0.081	N	0.34	neutral	None	None	None	None	N
Q/P	0.6483	likely_pathogenic	0.6996	pathogenic	0.146	Stabilizing	0.484	N	0.414	neutral	D	0.665281409	None	None	N
Q/R	0.1512	likely_benign	0.1621	benign	-0.473	Destabilizing	0.062	N	0.349	neutral	N	0.50863835	None	None	N
Q/S	0.2767	likely_benign	0.2805	benign	-1.138	Destabilizing	0.149	N	0.32	neutral	None	None	None	None	N
Q/T	0.2024	likely_benign	0.2079	benign	-0.834	Destabilizing	0.149	N	0.379	neutral	None	None	None	None	N
Q/V	0.2531	likely_benign	0.26	benign	0.146	Stabilizing	0.555	D	0.445	neutral	None	None	None	None	N
Q/W	0.6443	likely_pathogenic	0.6771	pathogenic	-0.216	Destabilizing	0.935	D	0.581	neutral	None	None	None	None	N
Q/Y	0.4427	ambiguous	0.4635	ambiguous	0.069	Stabilizing	0.235	N	0.443	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.