TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35751	107476;107477;107478	chr2:178528400;178528399;178528398	chr2:179393127;179393126;179393125
N2AB	34110	102553;102554;102555	chr2:178528400;178528399;178528398	chr2:179393127;179393126;179393125
N2A	33183	99772;99773;99774	chr2:178528400;178528399;178528398	chr2:179393127;179393126;179393125
N2B	26686	80281;80282;80283	chr2:178528400;178528399;178528398	chr2:179393127;179393126;179393125
Novex-1	26811	80656;80657;80658	chr2:178528400;178528399;178528398	chr2:179393127;179393126;179393125
Novex-2	26878	80857;80858;80859	chr2:178528400;178528399;178528398	chr2:179393127;179393126;179393125
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-168
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4458
• 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/R	None	None	0.009	N	0.187	0.191	0.126345400529	gnomAD-4.0.0	1.59141E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02371E-05

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	0.1231	likely_benign	0.1146	benign	-0.462	Destabilizing	0.25	N	0.315	neutral	None	None	None	None	I
S/C	0.2094	likely_benign	0.2164	benign	-0.281	Destabilizing	0.99	D	0.409	neutral	N	0.500179868	None	None	I
S/D	0.4405	ambiguous	0.4415	ambiguous	0.365	Stabilizing	0.447	N	0.256	neutral	None	None	None	None	I
S/E	0.5546	ambiguous	0.5314	ambiguous	0.289	Stabilizing	0.617	D	0.26	neutral	None	None	None	None	I
S/F	0.2386	likely_benign	0.1975	benign	-0.979	Destabilizing	0.92	D	0.481	neutral	None	None	None	None	I
S/G	0.1154	likely_benign	0.1235	benign	-0.6	Destabilizing	0.004	N	0.095	neutral	N	0.497677534	None	None	I
S/H	0.292	likely_benign	0.295	benign	-1.06	Destabilizing	0.85	D	0.397	neutral	None	None	None	None	I
S/I	0.1686	likely_benign	0.1677	benign	-0.223	Destabilizing	0.81	D	0.476	neutral	N	0.458255141	None	None	I
S/K	0.6017	likely_pathogenic	0.5885	pathogenic	-0.409	Destabilizing	0.447	N	0.279	neutral	None	None	None	None	I
S/L	0.1431	likely_benign	0.1274	benign	-0.223	Destabilizing	0.447	N	0.412	neutral	None	None	None	None	I
S/M	0.2644	likely_benign	0.2619	benign	-0.025	Destabilizing	0.992	D	0.387	neutral	None	None	None	None	I
S/N	0.1231	likely_benign	0.133	benign	-0.143	Destabilizing	0.004	N	0.098	neutral	N	0.482342722	None	None	I
S/P	0.8615	likely_pathogenic	0.8307	pathogenic	-0.273	Destabilizing	0.92	D	0.38	neutral	None	None	None	None	I
S/Q	0.4363	ambiguous	0.4433	ambiguous	-0.356	Destabilizing	0.85	D	0.354	neutral	None	None	None	None	I
S/R	0.4699	ambiguous	0.4685	ambiguous	-0.24	Destabilizing	0.009	N	0.187	neutral	N	0.428316236	None	None	I
S/T	0.0874	likely_benign	0.0863	benign	-0.269	Destabilizing	0.007	N	0.087	neutral	N	0.402687073	None	None	I
S/V	0.2231	likely_benign	0.2184	benign	-0.273	Destabilizing	0.447	N	0.42	neutral	None	None	None	None	I
S/W	0.4272	ambiguous	0.4012	ambiguous	-0.965	Destabilizing	0.992	D	0.575	neutral	None	None	None	None	I
S/Y	0.2329	likely_benign	0.2058	benign	-0.687	Destabilizing	0.972	D	0.48	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.