TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15925	47998;47999;48000	chr2:178617222;178617221;178617220	chr2:179481949;179481948;179481947
N2AB	14284	43075;43076;43077	chr2:178617222;178617221;178617220	chr2:179481949;179481948;179481947
N2A	13357	40294;40295;40296	chr2:178617222;178617221;178617220	chr2:179481949;179481948;179481947
N2B	6860	20803;20804;20805	chr2:178617222;178617221;178617220	chr2:179481949;179481948;179481947
Novex-1	6985	21178;21179;21180	chr2:178617222;178617221;178617220	chr2:179481949;179481948;179481947
Novex-2	7052	21379;21380;21381	chr2:178617222;178617221;178617220	chr2:179481949;179481948;179481947
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-3
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.5132
• 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/K	None	None	None	N	0.101	0.088	0.0762999501168	gnomAD-4.0.0	7.15785E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.24996E-07	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	0.1271	likely_benign	0.1432	benign	-0.583	Destabilizing	0.012	N	0.339	neutral	N	0.482026197	None	None	N
E/C	0.616	likely_pathogenic	0.6631	pathogenic	-0.242	Destabilizing	0.864	D	0.288	neutral	None	None	None	None	N
E/D	0.1623	likely_benign	0.207	benign	-0.527	Destabilizing	0.024	N	0.283	neutral	N	0.483310652	None	None	N
E/F	0.6008	likely_pathogenic	0.6654	pathogenic	-0.114	Destabilizing	0.628	D	0.303	neutral	None	None	None	None	N
E/G	0.1373	likely_benign	0.1622	benign	-0.847	Destabilizing	0.055	N	0.353	neutral	D	0.556607309	None	None	N
E/H	0.283	likely_benign	0.3175	benign	0.102	Stabilizing	0.214	N	0.262	neutral	None	None	None	None	N
E/I	0.1989	likely_benign	0.2238	benign	0.106	Stabilizing	0.356	N	0.322	neutral	None	None	None	None	N
E/K	0.0799	likely_benign	0.076	benign	0.185	Stabilizing	None	N	0.101	neutral	N	0.393191746	None	None	N
E/L	0.2105	likely_benign	0.2475	benign	0.106	Stabilizing	0.072	N	0.369	neutral	None	None	None	None	N
E/M	0.3002	likely_benign	0.3479	ambiguous	0.246	Stabilizing	0.356	N	0.303	neutral	None	None	None	None	N
E/N	0.1973	likely_benign	0.2403	benign	-0.398	Destabilizing	0.072	N	0.203	neutral	None	None	None	None	N
E/P	0.3585	ambiguous	0.3998	ambiguous	-0.103	Destabilizing	0.136	N	0.359	neutral	None	None	None	None	N
E/Q	0.0781	likely_benign	0.0841	benign	-0.303	Destabilizing	None	N	0.099	neutral	N	0.474145505	None	None	N
E/R	0.1249	likely_benign	0.1164	benign	0.51	Stabilizing	None	N	0.107	neutral	None	None	None	None	N
E/S	0.1721	likely_benign	0.1949	benign	-0.568	Destabilizing	0.016	N	0.285	neutral	None	None	None	None	N
E/T	0.1407	likely_benign	0.1636	benign	-0.334	Destabilizing	0.072	N	0.305	neutral	None	None	None	None	N
E/V	0.1261	likely_benign	0.1413	benign	-0.103	Destabilizing	0.055	N	0.344	neutral	N	0.462113801	None	None	N
E/W	0.7268	likely_pathogenic	0.7713	pathogenic	0.171	Stabilizing	0.864	D	0.296	neutral	None	None	None	None	N
E/Y	0.4561	ambiguous	0.5158	ambiguous	0.168	Stabilizing	0.356	N	0.311	neutral	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.