TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5717	17374;17375;17376	chr2:178731726;178731725;178731724	chr2:179596453;179596452;179596451
N2AB	5400	16423;16424;16425	chr2:178731726;178731725;178731724	chr2:179596453;179596452;179596451
N2A	4473	13642;13643;13644	chr2:178731726;178731725;178731724	chr2:179596453;179596452;179596451
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-40
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.3387
• 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
S/N	rs1484523576	-0.406	0.837	D	0.294	0.211	0.220303561663	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
S/N	rs1484523576	-0.406	0.837	D	0.294	0.211	0.220303561663	gnomAD-4.0.0	9.5843E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.25991E-05	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	0.1022	likely_benign	0.0963	benign	-0.493	Destabilizing	0.737	D	0.287	neutral	None	None	None	None	I
S/C	0.1477	likely_benign	0.1504	benign	-0.386	Destabilizing	0.998	D	0.517	neutral	N	0.502408367	None	None	I
S/D	0.4032	ambiguous	0.317	benign	0.107	Stabilizing	0.872	D	0.286	neutral	None	None	None	None	I
S/E	0.5051	ambiguous	0.4053	ambiguous	0.026	Stabilizing	0.584	D	0.335	neutral	None	None	None	None	I
S/F	0.196	likely_benign	0.1836	benign	-0.961	Destabilizing	0.98	D	0.63	neutral	None	None	None	None	I
S/G	0.1028	likely_benign	0.1066	benign	-0.633	Destabilizing	0.811	D	0.305	neutral	N	0.49464646	None	None	I
S/H	0.3414	ambiguous	0.2918	benign	-1.12	Destabilizing	0.047	N	0.301	neutral	None	None	None	None	I
S/I	0.1885	likely_benign	0.1788	benign	-0.249	Destabilizing	0.947	D	0.599	neutral	N	0.485367296	None	None	I
S/K	0.655	likely_pathogenic	0.5554	ambiguous	-0.562	Destabilizing	0.083	N	0.115	neutral	None	None	None	None	I
S/L	0.1378	likely_benign	0.1346	benign	-0.249	Destabilizing	0.872	D	0.579	neutral	None	None	None	None	I
S/M	0.2331	likely_benign	0.2223	benign	0.023	Stabilizing	0.993	D	0.53	neutral	None	None	None	None	I
S/N	0.1249	likely_benign	0.1172	benign	-0.297	Destabilizing	0.837	D	0.294	neutral	D	0.52470942	None	None	I
S/P	0.6756	likely_pathogenic	0.6634	pathogenic	-0.3	Destabilizing	0.977	D	0.486	neutral	None	None	None	None	I
S/Q	0.4903	ambiguous	0.4162	ambiguous	-0.571	Destabilizing	0.209	N	0.231	neutral	None	None	None	None	I
S/R	0.5558	ambiguous	0.4621	ambiguous	-0.34	Destabilizing	0.016	N	0.266	neutral	N	0.501467201	None	None	I
S/T	0.0877	likely_benign	0.083	benign	-0.426	Destabilizing	0.064	N	0.13	neutral	N	0.481361287	None	None	I
S/V	0.1937	likely_benign	0.1854	benign	-0.3	Destabilizing	0.872	D	0.57	neutral	None	None	None	None	I
S/W	0.4176	ambiguous	0.381	ambiguous	-0.914	Destabilizing	0.998	D	0.638	neutral	None	None	None	None	I
S/Y	0.2014	likely_benign	0.179	benign	-0.659	Destabilizing	0.96	D	0.608	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.