TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29890	89893;89894;89895	chr2:178553232;178553231;178553230	chr2:179417959;179417958;179417957
N2AB	28249	84970;84971;84972	chr2:178553232;178553231;178553230	chr2:179417959;179417958;179417957
N2A	27322	82189;82190;82191	chr2:178553232;178553231;178553230	chr2:179417959;179417958;179417957
N2B	20825	62698;62699;62700	chr2:178553232;178553231;178553230	chr2:179417959;179417958;179417957
Novex-1	20950	63073;63074;63075	chr2:178553232;178553231;178553230	chr2:179417959;179417958;179417957
Novex-2	21017	63274;63275;63276	chr2:178553232;178553231;178553230	chr2:179417959;179417958;179417957
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-147
• Domain position: 49
• Structural Position: 127
• Q(SASA): 0.4458
• 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
N/D	None	None	0.98	N	0.619	0.31	0.416328079214	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.36	ambiguous	0.3419	ambiguous	-0.536	Destabilizing	0.971	D	0.661	neutral	None	None	None	None	N
N/C	0.3459	ambiguous	0.3519	ambiguous	0.258	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
N/D	0.2647	likely_benign	0.2312	benign	0.029	Stabilizing	0.98	D	0.619	neutral	N	0.499234972	None	None	N
N/E	0.5332	ambiguous	0.4876	ambiguous	0.018	Stabilizing	0.985	D	0.628	neutral	None	None	None	None	N
N/F	0.6714	likely_pathogenic	0.6395	pathogenic	-0.773	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
N/G	0.471	ambiguous	0.445	ambiguous	-0.75	Destabilizing	0.985	D	0.585	neutral	None	None	None	None	N
N/H	0.1715	likely_benign	0.157	benign	-0.751	Destabilizing	0.999	D	0.669	neutral	D	0.533251545	None	None	N
N/I	0.2355	likely_benign	0.216	benign	-0.051	Destabilizing	0.994	D	0.785	deleterious	D	0.526978934	None	None	N
N/K	0.4326	ambiguous	0.395	ambiguous	0.048	Stabilizing	0.98	D	0.631	neutral	N	0.502061847	None	None	N
N/L	0.3277	likely_benign	0.3142	benign	-0.051	Destabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	N
N/M	0.3355	likely_benign	0.3252	benign	0.39	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
N/P	0.7799	likely_pathogenic	0.7504	pathogenic	-0.185	Destabilizing	0.998	D	0.772	deleterious	None	None	None	None	N
N/Q	0.4425	ambiguous	0.4227	ambiguous	-0.517	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
N/R	0.5209	ambiguous	0.4907	ambiguous	0.082	Stabilizing	0.998	D	0.649	neutral	None	None	None	None	N
N/S	0.1298	likely_benign	0.1275	benign	-0.315	Destabilizing	0.659	D	0.357	neutral	N	0.449787587	None	None	N
N/T	0.1253	likely_benign	0.1228	benign	-0.164	Destabilizing	0.4	N	0.363	neutral	N	0.429124313	None	None	N
N/V	0.2448	likely_benign	0.2308	benign	-0.185	Destabilizing	0.996	D	0.742	deleterious	None	None	None	None	N
N/W	0.8602	likely_pathogenic	0.8377	pathogenic	-0.658	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
N/Y	0.2146	likely_benign	0.1942	benign	-0.421	Destabilizing	0.999	D	0.766	deleterious	D	0.524938706	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.