TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23836	71731;71732;71733	chr2:178574626;178574625;178574624	chr2:179439353;179439352;179439351
N2AB	22195	66808;66809;66810	chr2:178574626;178574625;178574624	chr2:179439353;179439352;179439351
N2A	21268	64027;64028;64029	chr2:178574626;178574625;178574624	chr2:179439353;179439352;179439351
N2B	14771	44536;44537;44538	chr2:178574626;178574625;178574624	chr2:179439353;179439352;179439351
Novex-1	14896	44911;44912;44913	chr2:178574626;178574625;178574624	chr2:179439353;179439352;179439351
Novex-2	14963	45112;45113;45114	chr2:178574626;178574625;178574624	chr2:179439353;179439352;179439351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-61
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3941
• 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
T/S	None	None	0.027	N	0.353	0.084	0.137902524267	gnomAD-4.0.0	1.59271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86067E-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
T/A	0.0825	likely_benign	0.0726	benign	-0.351	Destabilizing	None	N	0.071	neutral	N	0.480560706	None	None	N
T/C	0.3208	likely_benign	0.2951	benign	-0.262	Destabilizing	0.555	D	0.439	neutral	None	None	None	None	N
T/D	0.337	likely_benign	0.3261	benign	0.17	Stabilizing	0.38	N	0.497	neutral	None	None	None	None	N
T/E	0.2525	likely_benign	0.2267	benign	0.091	Stabilizing	0.149	N	0.467	neutral	None	None	None	None	N
T/F	0.1532	likely_benign	0.1324	benign	-0.847	Destabilizing	0.38	N	0.495	neutral	None	None	None	None	N
T/G	0.2101	likely_benign	0.1939	benign	-0.476	Destabilizing	0.081	N	0.457	neutral	None	None	None	None	N
T/H	0.2143	likely_benign	0.2004	benign	-0.762	Destabilizing	0.935	D	0.434	neutral	None	None	None	None	N
T/I	0.0823	likely_benign	0.071	benign	-0.144	Destabilizing	None	N	0.139	neutral	N	0.495028726	None	None	N
T/K	0.1841	likely_benign	0.1679	benign	-0.334	Destabilizing	0.149	N	0.462	neutral	None	None	None	None	N
T/L	0.0605	likely_benign	0.0569	benign	-0.144	Destabilizing	0.005	N	0.239	neutral	None	None	None	None	N
T/M	0.0688	likely_benign	0.0642	benign	0.04	Stabilizing	0.005	N	0.247	neutral	None	None	None	None	N
T/N	0.1131	likely_benign	0.111	benign	-0.129	Destabilizing	0.484	N	0.449	neutral	N	0.470789808	None	None	N
T/P	0.2715	likely_benign	0.2389	benign	-0.185	Destabilizing	0.317	N	0.51	neutral	N	0.475171127	None	None	N
T/Q	0.2017	likely_benign	0.1873	benign	-0.375	Destabilizing	0.555	D	0.485	neutral	None	None	None	None	N
T/R	0.1596	likely_benign	0.1434	benign	-0.048	Destabilizing	0.38	N	0.508	neutral	None	None	None	None	N
T/S	0.1018	likely_benign	0.0981	benign	-0.346	Destabilizing	0.027	N	0.353	neutral	N	0.414775644	None	None	N
T/V	0.0792	likely_benign	0.0709	benign	-0.185	Destabilizing	0.001	N	0.067	neutral	None	None	None	None	N
T/W	0.506	ambiguous	0.4575	ambiguous	-0.843	Destabilizing	0.935	D	0.475	neutral	None	None	None	None	N
T/Y	0.2251	likely_benign	0.1996	benign	-0.559	Destabilizing	0.555	D	0.499	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.