TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5551	16876;16877;16878	chr2:178732318;178732317;178732316	chr2:179597045;179597044;179597043
N2AB	5234	15925;15926;15927	chr2:178732318;178732317;178732316	chr2:179597045;179597044;179597043
N2A	4307	13144;13145;13146	chr2:178732318;178732317;178732316	chr2:179597045;179597044;179597043
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-39
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6481
• 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
P/L	rs762729065	0.097	None	N	0.204	0.135	0.269111216191	gnomAD-2.1.1	4.11E-06	None	None	None	None	I	None	0	0	None	1.04188E-04	0	None	0	None	0	0	0
P/L	rs762729065	0.097	None	N	0.204	0.135	0.269111216191	gnomAD-4.0.0	1.61106E-06	None	None	None	None	I	None	0	0	None	4.85767E-05	0	None	0	0	0	0	0
P/T	rs1578181149	None	0.062	N	0.289	0.061	0.177238962908	gnomAD-4.0.0	1.08029E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.18125E-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
P/A	0.0708	likely_benign	0.0639	benign	-0.302	Destabilizing	0.001	N	0.123	neutral	N	0.460422215	None	None	I
P/C	0.3906	ambiguous	0.3226	benign	-0.628	Destabilizing	0.935	D	0.387	neutral	None	None	None	None	I
P/D	0.2882	likely_benign	0.2239	benign	0.048	Stabilizing	0.149	N	0.335	neutral	None	None	None	None	I
P/E	0.2195	likely_benign	0.1752	benign	-0.069	Destabilizing	0.149	N	0.333	neutral	None	None	None	None	I
P/F	0.3156	likely_benign	0.2454	benign	-0.579	Destabilizing	0.235	N	0.419	neutral	None	None	None	None	I
P/G	0.2109	likely_benign	0.1765	benign	-0.406	Destabilizing	0.081	N	0.328	neutral	None	None	None	None	I
P/H	0.1427	likely_benign	0.1122	benign	-0.037	Destabilizing	0.824	D	0.38	neutral	None	None	None	None	I
P/I	0.2083	likely_benign	0.1674	benign	-0.187	Destabilizing	0.081	N	0.411	neutral	None	None	None	None	I
P/K	0.2198	likely_benign	0.1657	benign	-0.23	Destabilizing	0.081	N	0.305	neutral	None	None	None	None	I
P/L	0.0952	likely_benign	0.0803	benign	-0.187	Destabilizing	None	N	0.204	neutral	N	0.500999401	None	None	I
P/M	0.2289	likely_benign	0.19	benign	-0.303	Destabilizing	0.235	N	0.387	neutral	None	None	None	None	I
P/N	0.1954	likely_benign	0.1567	benign	-0.004	Destabilizing	0.235	N	0.381	neutral	None	None	None	None	I
P/Q	0.1258	likely_benign	0.1023	benign	-0.223	Destabilizing	0.317	N	0.333	neutral	N	0.508984166	None	None	I
P/R	0.1538	likely_benign	0.1167	benign	0.205	Stabilizing	0.317	N	0.381	neutral	N	0.495073506	None	None	I
P/S	0.0958	likely_benign	0.0789	benign	-0.384	Destabilizing	0.002	N	0.164	neutral	N	0.450261149	None	None	I
P/T	0.0867	likely_benign	0.0743	benign	-0.4	Destabilizing	0.062	N	0.289	neutral	N	0.466462753	None	None	I
P/V	0.152	likely_benign	0.1312	benign	-0.191	Destabilizing	0.035	N	0.325	neutral	None	None	None	None	I
P/W	0.4576	ambiguous	0.3662	ambiguous	-0.654	Destabilizing	0.935	D	0.455	neutral	None	None	None	None	I
P/Y	0.2795	likely_benign	0.2144	benign	-0.344	Destabilizing	0.555	D	0.411	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.