TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26630	80113;80114;80115	chr2:178566244;178566243;178566242	chr2:179430971;179430970;179430969
N2AB	24989	75190;75191;75192	chr2:178566244;178566243;178566242	chr2:179430971;179430970;179430969
N2A	24062	72409;72410;72411	chr2:178566244;178566243;178566242	chr2:179430971;179430970;179430969
N2B	17565	52918;52919;52920	chr2:178566244;178566243;178566242	chr2:179430971;179430970;179430969
Novex-1	17690	53293;53294;53295	chr2:178566244;178566243;178566242	chr2:179430971;179430970;179430969
Novex-2	17757	53494;53495;53496	chr2:178566244;178566243;178566242	chr2:179430971;179430970;179430969
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: Ig-138
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.9868
• 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
E/D	None	None	0.002	N	0.196	0.069	0.104622674875	gnomAD-4.0.0	1.36852E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79907E-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	0.1151	likely_benign	0.104	benign	-0.027	Destabilizing	0.822	D	0.467	neutral	N	0.501980836	None	None	I
E/C	0.7268	likely_pathogenic	0.6664	pathogenic	-0.024	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	I
E/D	0.0644	likely_benign	0.064	benign	-0.263	Destabilizing	0.002	N	0.196	neutral	N	0.367914699	None	None	I
E/F	0.6308	likely_pathogenic	0.5526	ambiguous	-0.068	Destabilizing	0.993	D	0.558	neutral	None	None	None	None	I
E/G	0.1017	likely_benign	0.0915	benign	-0.154	Destabilizing	0.822	D	0.469	neutral	N	0.360633649	None	None	I
E/H	0.3886	ambiguous	0.3508	ambiguous	0.411	Stabilizing	0.993	D	0.453	neutral	None	None	None	None	I
E/I	0.2832	likely_benign	0.2403	benign	0.252	Stabilizing	0.978	D	0.544	neutral	None	None	None	None	I
E/K	0.1655	likely_benign	0.1407	benign	0.553	Stabilizing	0.822	D	0.473	neutral	N	0.479834695	None	None	I
E/L	0.3483	ambiguous	0.2979	benign	0.252	Stabilizing	0.978	D	0.534	neutral	None	None	None	None	I
E/M	0.3789	ambiguous	0.3423	ambiguous	0.107	Stabilizing	0.998	D	0.522	neutral	None	None	None	None	I
E/N	0.1368	likely_benign	0.1212	benign	0.312	Stabilizing	0.754	D	0.44	neutral	None	None	None	None	I
E/P	0.4219	ambiguous	0.3732	ambiguous	0.178	Stabilizing	0.978	D	0.442	neutral	None	None	None	None	I
E/Q	0.1673	likely_benign	0.155	benign	0.315	Stabilizing	0.904	D	0.439	neutral	N	0.489494328	None	None	I
E/R	0.2895	likely_benign	0.2551	benign	0.722	Stabilizing	0.978	D	0.452	neutral	None	None	None	None	I
E/S	0.1395	likely_benign	0.126	benign	0.177	Stabilizing	0.86	D	0.454	neutral	None	None	None	None	I
E/T	0.1482	likely_benign	0.1327	benign	0.286	Stabilizing	0.86	D	0.431	neutral	None	None	None	None	I
E/V	0.1829	likely_benign	0.1578	benign	0.178	Stabilizing	0.97	D	0.461	neutral	N	0.459757492	None	None	I
E/W	0.8184	likely_pathogenic	0.7697	pathogenic	-0.011	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	I
E/Y	0.4557	ambiguous	0.3986	ambiguous	0.165	Stabilizing	0.993	D	0.515	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.