TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8143	24652;24653;24654	chr2:178718773;178718772;178718771	chr2:179583500;179583499;179583498
N2AB	7826	23701;23702;23703	chr2:178718773;178718772;178718771	chr2:179583500;179583499;179583498
N2A	6899	20920;20921;20922	chr2:178718773;178718772;178718771	chr2:179583500;179583499;179583498
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-66
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.6122
• Predicted PPI site: I

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
L/I	rs1274064527	-0.016	0.007	N	0.193	0.028	0.104622674875	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/I	rs1274064527	-0.016	0.007	N	0.193	0.028	0.104622674875	gnomAD-4.0.0	1.36843E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79898E-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
L/A	0.0693	likely_benign	0.0643	benign	-0.446	Destabilizing	None	N	0.105	neutral	None	None	None	None	I
L/C	0.3417	ambiguous	0.2989	benign	-0.73	Destabilizing	0.245	N	0.249	neutral	None	None	None	None	I
L/D	0.1982	likely_benign	0.1947	benign	-0.204	Destabilizing	0.022	N	0.365	neutral	None	None	None	None	I
L/E	0.1115	likely_benign	0.1141	benign	-0.299	Destabilizing	0.009	N	0.321	neutral	None	None	None	None	I
L/F	0.0785	likely_benign	0.0762	benign	-0.578	Destabilizing	None	N	0.13	neutral	N	0.483875078	None	None	I
L/G	0.1289	likely_benign	0.1276	benign	-0.562	Destabilizing	None	N	0.127	neutral	None	None	None	None	I
L/H	0.1069	likely_benign	0.0974	benign	0.089	Stabilizing	0.245	N	0.293	neutral	None	None	None	None	I
L/I	0.0778	likely_benign	0.0747	benign	-0.267	Destabilizing	0.007	N	0.193	neutral	N	0.483605719	None	None	I
L/K	0.1092	likely_benign	0.1094	benign	-0.319	Destabilizing	0.009	N	0.269	neutral	None	None	None	None	I
L/M	0.0853	likely_benign	0.0819	benign	-0.495	Destabilizing	0.004	N	0.163	neutral	None	None	None	None	I
L/N	0.1162	likely_benign	0.1177	benign	-0.174	Destabilizing	0.022	N	0.367	neutral	None	None	None	None	I
L/P	0.1177	likely_benign	0.1203	benign	-0.297	Destabilizing	None	N	0.183	neutral	None	None	None	None	I
L/Q	0.0736	likely_benign	0.0711	benign	-0.363	Destabilizing	0.044	N	0.359	neutral	None	None	None	None	I
L/R	0.0895	likely_benign	0.0861	benign	0.172	Stabilizing	0.044	N	0.391	neutral	None	None	None	None	I
L/S	0.065	likely_benign	0.0607	benign	-0.569	Destabilizing	None	N	0.097	neutral	N	0.342514822	None	None	I
L/T	0.0785	likely_benign	0.0762	benign	-0.559	Destabilizing	None	N	0.137	neutral	None	None	None	None	I
L/V	0.0722	likely_benign	0.0676	benign	-0.297	Destabilizing	0.007	N	0.165	neutral	N	0.468617624	None	None	I
L/W	0.1233	likely_benign	0.1194	benign	-0.604	Destabilizing	0.788	D	0.28	neutral	None	None	None	None	I
L/Y	0.1913	likely_benign	0.1746	benign	-0.36	Destabilizing	0.022	N	0.319	neutral	None	None	None	None	I

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.