TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20790	62593;62594;62595	chr2:178589357;178589356;178589355	chr2:179454084;179454083;179454082
N2AB	19149	57670;57671;57672	chr2:178589357;178589356;178589355	chr2:179454084;179454083;179454082
N2A	18222	54889;54890;54891	chr2:178589357;178589356;178589355	chr2:179454084;179454083;179454082
N2B	11725	35398;35399;35400	chr2:178589357;178589356;178589355	chr2:179454084;179454083;179454082
Novex-1	11850	35773;35774;35775	chr2:178589357;178589356;178589355	chr2:179454084;179454083;179454082
Novex-2	11917	35974;35975;35976	chr2:178589357;178589356;178589355	chr2:179454084;179454083;179454082
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-122
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.342
• 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
E/A	None	None	0.996	N	0.515	0.612	0.541875726618	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
E/A	0.368	ambiguous	0.3602	ambiguous	-0.814	Destabilizing	0.996	D	0.515	neutral	N	0.501987276	None	None	N
E/C	0.9404	likely_pathogenic	0.9478	pathogenic	-0.364	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
E/D	0.1916	likely_benign	0.206	benign	-1.153	Destabilizing	0.998	D	0.425	neutral	N	0.460775371	None	None	N
E/F	0.902	likely_pathogenic	0.9101	pathogenic	-0.457	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/G	0.5347	ambiguous	0.5263	ambiguous	-1.159	Destabilizing	0.999	D	0.677	prob.neutral	D	0.523498698	None	None	N
E/H	0.7508	likely_pathogenic	0.7534	pathogenic	-0.756	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
E/I	0.5843	likely_pathogenic	0.6047	pathogenic	0.117	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/K	0.5886	likely_pathogenic	0.571	pathogenic	-0.45	Destabilizing	0.767	D	0.395	neutral	N	0.464930397	None	None	N
E/L	0.6762	likely_pathogenic	0.7005	pathogenic	0.117	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/M	0.7244	likely_pathogenic	0.7295	pathogenic	0.575	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/N	0.5665	likely_pathogenic	0.5707	pathogenic	-0.887	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
E/P	0.9615	likely_pathogenic	0.9625	pathogenic	-0.172	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/Q	0.3172	likely_benign	0.2964	benign	-0.784	Destabilizing	0.996	D	0.57	neutral	N	0.48036121	None	None	N
E/R	0.7052	likely_pathogenic	0.6767	pathogenic	-0.262	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
E/S	0.4252	ambiguous	0.4232	ambiguous	-1.178	Destabilizing	0.997	D	0.515	neutral	None	None	None	None	N
E/T	0.4088	ambiguous	0.4128	ambiguous	-0.89	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/V	0.3768	ambiguous	0.3834	ambiguous	-0.172	Destabilizing	0.999	D	0.707	prob.neutral	N	0.494042583	None	None	N
E/W	0.9648	likely_pathogenic	0.9645	pathogenic	-0.249	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/Y	0.8676	likely_pathogenic	0.8715	pathogenic	-0.2	Destabilizing	1.0	D	0.741	deleterious	None	None	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.