TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26828	80707;80708;80709	chr2:178565650;178565649;178565648	chr2:179430377;179430376;179430375
N2AB	25187	75784;75785;75786	chr2:178565650;178565649;178565648	chr2:179430377;179430376;179430375
N2A	24260	73003;73004;73005	chr2:178565650;178565649;178565648	chr2:179430377;179430376;179430375
N2B	17763	53512;53513;53514	chr2:178565650;178565649;178565648	chr2:179430377;179430376;179430375
Novex-1	17888	53887;53888;53889	chr2:178565650;178565649;178565648	chr2:179430377;179430376;179430375
Novex-2	17955	54088;54089;54090	chr2:178565650;178565649;178565648	chr2:179430377;179430376;179430375
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-83
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4738
• 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
S/N	None	None	None	N	0.177	0.072	0.152612264143	gnomAD-4.0.0	2.05283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79913E-06	1.15937E-05	0
S/R	rs886055243	None	0.171	N	0.449	0.157	0.0806252709748	gnomAD-4.0.0	4.77485E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.5776E-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
S/A	0.0842	likely_benign	0.0762	benign	-0.517	Destabilizing	0.014	N	0.236	neutral	None	None	None	None	N
S/C	0.1008	likely_benign	0.1199	benign	-0.354	Destabilizing	0.828	D	0.411	neutral	D	0.522079254	None	None	N
S/D	0.2998	likely_benign	0.3438	ambiguous	0.101	Stabilizing	0.038	N	0.197	neutral	None	None	None	None	N
S/E	0.3709	ambiguous	0.4129	ambiguous	0.109	Stabilizing	0.038	N	0.189	neutral	None	None	None	None	N
S/F	0.2122	likely_benign	0.1775	benign	-0.662	Destabilizing	0.214	N	0.446	neutral	None	None	None	None	N
S/G	0.083	likely_benign	0.0946	benign	-0.765	Destabilizing	None	N	0.1	neutral	N	0.484561016	None	None	N
S/H	0.2452	likely_benign	0.3104	benign	-1.118	Destabilizing	0.214	N	0.419	neutral	None	None	None	None	N
S/I	0.1182	likely_benign	0.1292	benign	0.035	Stabilizing	None	N	0.167	neutral	N	0.38170322	None	None	N
S/K	0.4952	ambiguous	0.5951	pathogenic	-0.55	Destabilizing	0.038	N	0.189	neutral	None	None	None	None	N
S/L	0.1065	likely_benign	0.0921	benign	0.035	Stabilizing	0.006	N	0.396	neutral	None	None	None	None	N
S/M	0.1323	likely_benign	0.1363	benign	0.017	Stabilizing	0.214	N	0.427	neutral	None	None	None	None	N
S/N	0.0814	likely_benign	0.1009	benign	-0.507	Destabilizing	None	N	0.177	neutral	N	0.444866477	None	None	N
S/P	0.7702	likely_pathogenic	0.753	pathogenic	-0.115	Destabilizing	0.356	N	0.449	neutral	None	None	None	None	N
S/Q	0.3416	ambiguous	0.4176	ambiguous	-0.561	Destabilizing	0.214	N	0.33	neutral	None	None	None	None	N
S/R	0.4537	ambiguous	0.5548	ambiguous	-0.47	Destabilizing	0.171	N	0.449	neutral	N	0.416642513	None	None	N
S/T	0.0702	likely_benign	0.07	benign	-0.509	Destabilizing	0.001	N	0.127	neutral	N	0.378124197	None	None	N
S/V	0.12	likely_benign	0.1223	benign	-0.115	Destabilizing	0.001	N	0.214	neutral	None	None	None	None	N
S/W	0.3737	ambiguous	0.3658	ambiguous	-0.723	Destabilizing	0.864	D	0.456	neutral	None	None	None	None	N
S/Y	0.1779	likely_benign	0.1733	benign	-0.423	Destabilizing	0.356	N	0.434	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.