TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8882	26869;26870;26871	chr2:178714014;178714013;178714012	chr2:179578741;179578740;179578739
N2AB	8565	25918;25919;25920	chr2:178714014;178714013;178714012	chr2:179578741;179578740;179578739
N2A	7638	23137;23138;23139	chr2:178714014;178714013;178714012	chr2:179578741;179578740;179578739
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-74
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.5866
• 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
N/S	rs1035818414	None	0.826	N	0.279	0.192	0.132336055621	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	1.09649E-03	0	0	None	0	0	0	0	0
N/S	rs1035818414	None	0.826	N	0.279	0.192	0.132336055621	gnomAD-4.0.0	6.57177E-06	None	None	None	None	N	None	0	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
N/A	0.3688	ambiguous	0.4537	ambiguous	-0.075	Destabilizing	0.863	D	0.305	neutral	None	None	None	None	N
N/C	0.38	ambiguous	0.5062	ambiguous	-0.058	Destabilizing	0.999	D	0.267	neutral	None	None	None	None	N
N/D	0.1484	likely_benign	0.1764	benign	0.233	Stabilizing	0.704	D	0.271	neutral	N	0.421709111	None	None	N
N/E	0.4268	ambiguous	0.4785	ambiguous	0.198	Stabilizing	0.17	N	0.098	neutral	None	None	None	None	N
N/F	0.7163	likely_pathogenic	0.8072	pathogenic	-0.709	Destabilizing	0.997	D	0.257	neutral	None	None	None	None	N
N/G	0.2286	likely_benign	0.2698	benign	-0.176	Destabilizing	0.927	D	0.237	neutral	None	None	None	None	N
N/H	0.0857	likely_benign	0.1048	benign	-0.098	Destabilizing	0.988	D	0.267	neutral	N	0.492187917	None	None	N
N/I	0.6012	likely_pathogenic	0.7195	pathogenic	0.094	Stabilizing	0.996	D	0.297	neutral	N	0.46550471	None	None	N
N/K	0.2884	likely_benign	0.3499	ambiguous	0.144	Stabilizing	0.704	D	0.263	neutral	N	0.449127786	None	None	N
N/L	0.353	ambiguous	0.4383	ambiguous	0.094	Stabilizing	0.939	D	0.341	neutral	None	None	None	None	N
N/M	0.5322	ambiguous	0.6353	pathogenic	-0.126	Destabilizing	0.997	D	0.237	neutral	None	None	None	None	N
N/P	0.742	likely_pathogenic	0.7933	pathogenic	0.061	Stabilizing	0.997	D	0.324	neutral	None	None	None	None	N
N/Q	0.2555	likely_benign	0.294	benign	-0.293	Destabilizing	0.2	N	0.1	neutral	None	None	None	None	N
N/R	0.2694	likely_benign	0.3239	benign	0.232	Stabilizing	0.02	N	0.09	neutral	None	None	None	None	N
N/S	0.0876	likely_benign	0.1002	benign	-0.148	Destabilizing	0.826	D	0.279	neutral	N	0.505365071	None	None	N
N/T	0.2989	likely_benign	0.3837	ambiguous	-0.06	Destabilizing	0.959	D	0.22	neutral	N	0.496150942	None	None	N
N/V	0.5893	likely_pathogenic	0.7004	pathogenic	0.061	Stabilizing	0.969	D	0.341	neutral	None	None	None	None	N
N/W	0.7489	likely_pathogenic	0.8242	pathogenic	-0.878	Destabilizing	0.999	D	0.304	neutral	None	None	None	None	N
N/Y	0.2015	likely_benign	0.2682	benign	-0.516	Destabilizing	0.996	D	0.272	neutral	N	0.454148405	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.