TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15345	46258;46259;46260	chr2:178620488;178620487;178620486	chr2:179485215;179485214;179485213
N2AB	13704	41335;41336;41337	chr2:178620488;178620487;178620486	chr2:179485215;179485214;179485213
N2A	12777	38554;38555;38556	chr2:178620488;178620487;178620486	chr2:179485215;179485214;179485213
N2B	6280	19063;19064;19065	chr2:178620488;178620487;178620486	chr2:179485215;179485214;179485213
Novex-1	6405	19438;19439;19440	chr2:178620488;178620487;178620486	chr2:179485215;179485214;179485213
Novex-2	6472	19639;19640;19641	chr2:178620488;178620487;178620486	chr2:179485215;179485214;179485213
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-105
• Domain position: 44
• Structural Position: 111
• Q(SASA): 0.9301
• 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/K	None	None	None	N	0.114	0.11	0.0884992946249	gnomAD-4.0.0	1.3695E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80005E-06	0	0
N/S	None	None	0.101	N	0.299	0.097	0.126345400529	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
N/A	0.1994	likely_benign	0.1816	benign	-0.099	Destabilizing	0.129	N	0.321	neutral	None	None	None	None	N
N/C	0.2923	likely_benign	0.3231	benign	0.203	Stabilizing	0.983	D	0.291	neutral	None	None	None	None	N
N/D	0.1472	likely_benign	0.1186	benign	0.079	Stabilizing	0.183	N	0.274	neutral	N	0.390664343	None	None	N
N/E	0.2637	likely_benign	0.245	benign	0.012	Stabilizing	0.129	N	0.269	neutral	None	None	None	None	N
N/F	0.5589	ambiguous	0.6124	pathogenic	-0.726	Destabilizing	0.94	D	0.308	neutral	None	None	None	None	N
N/G	0.2024	likely_benign	0.1939	benign	-0.181	Destabilizing	0.228	N	0.307	neutral	None	None	None	None	N
N/H	0.0974	likely_benign	0.0914	benign	-0.24	Destabilizing	0.794	D	0.301	neutral	N	0.444652131	None	None	N
N/I	0.2518	likely_benign	0.2632	benign	0.018	Stabilizing	0.794	D	0.349	neutral	N	0.454089933	None	None	N
N/K	0.1346	likely_benign	0.1239	benign	0.147	Stabilizing	None	N	0.114	neutral	N	0.327643957	None	None	N
N/L	0.2161	likely_benign	0.2348	benign	0.018	Stabilizing	0.418	N	0.347	neutral	None	None	None	None	N
N/M	0.3504	ambiguous	0.3582	ambiguous	0.147	Stabilizing	0.94	D	0.301	neutral	None	None	None	None	N
N/P	0.2856	likely_benign	0.2925	benign	0.001	Stabilizing	0.593	D	0.339	neutral	None	None	None	None	N
N/Q	0.2038	likely_benign	0.1909	benign	-0.207	Destabilizing	0.264	N	0.252	neutral	None	None	None	None	N
N/R	0.1434	likely_benign	0.1684	benign	0.205	Stabilizing	0.001	N	0.141	neutral	None	None	None	None	N
N/S	0.0801	likely_benign	0.0665	benign	0.019	Stabilizing	0.101	N	0.299	neutral	N	0.425794006	None	None	N
N/T	0.138	likely_benign	0.1232	benign	0.062	Stabilizing	0.183	N	0.249	neutral	N	0.436405671	None	None	N
N/V	0.2679	likely_benign	0.2578	benign	0.001	Stabilizing	0.418	N	0.389	neutral	None	None	None	None	N
N/W	0.6397	likely_pathogenic	0.7045	pathogenic	-0.865	Destabilizing	0.983	D	0.317	neutral	None	None	None	None	N
N/Y	0.1775	likely_benign	0.1978	benign	-0.534	Destabilizing	0.921	D	0.327	neutral	N	0.453246956	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.