TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3873	11842;11843;11844	chr2:178741616;178741615;178741614	chr2:179606343;179606342;179606341
N2AB	3556	10891;10892;10893	chr2:178741616;178741615;178741614	chr2:179606343;179606342;179606341
N2A	None	None	chr2:None	chr2:None
N2B	3510	10753;10754;10755	chr2:178741616;178741615;178741614	chr2:179606343;179606342;179606341
Novex-1	3635	11128;11129;11130	chr2:178741616;178741615;178741614	chr2:179606343;179606342;179606341
Novex-2	3702	11329;11330;11331	chr2:178741616;178741615;178741614	chr2:179606343;179606342;179606341
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-27
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.471
• 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
D/H	rs1435923406	None	0.317	N	0.543	0.143	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/H	rs1435923406	None	0.317	N	0.543	0.143	None	gnomAD-4.0.0	6.57186E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46994E-05	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
D/A	0.1432	likely_benign	0.1393	benign	-0.423	Destabilizing	0.052	N	0.489	neutral	N	0.489227862	None	None	I
D/C	0.3528	ambiguous	0.4071	ambiguous	-0.233	Destabilizing	0.935	D	0.581	neutral	None	None	None	None	I
D/E	0.1816	likely_benign	0.173	benign	-0.61	Destabilizing	None	N	0.119	neutral	N	0.449978695	None	None	I
D/F	0.3627	ambiguous	0.3786	ambiguous	0.169	Stabilizing	0.791	D	0.576	neutral	None	None	None	None	I
D/G	0.1319	likely_benign	0.1324	benign	-0.802	Destabilizing	0.027	N	0.407	neutral	N	0.437238869	None	None	I
D/H	0.1693	likely_benign	0.1676	benign	-0.148	Destabilizing	0.317	N	0.543	neutral	N	0.509376121	None	None	I
D/I	0.2356	likely_benign	0.236	benign	0.585	Stabilizing	0.555	D	0.593	neutral	None	None	None	None	I
D/K	0.2178	likely_benign	0.2086	benign	-0.425	Destabilizing	0.035	N	0.415	neutral	None	None	None	None	I
D/L	0.2774	likely_benign	0.2783	benign	0.585	Stabilizing	0.149	N	0.571	neutral	None	None	None	None	I
D/M	0.4485	ambiguous	0.4321	ambiguous	0.958	Stabilizing	0.935	D	0.558	neutral	None	None	None	None	I
D/N	0.0647	likely_benign	0.0614	benign	-0.944	Destabilizing	None	N	0.129	neutral	N	0.455632698	None	None	I
D/P	0.5995	likely_pathogenic	0.6203	pathogenic	0.275	Stabilizing	0.555	D	0.53	neutral	None	None	None	None	I
D/Q	0.262	likely_benign	0.2481	benign	-0.747	Destabilizing	0.081	N	0.45	neutral	None	None	None	None	I
D/R	0.2097	likely_benign	0.2124	benign	-0.201	Destabilizing	0.149	N	0.569	neutral	None	None	None	None	I
D/S	0.0962	likely_benign	0.0908	benign	-1.189	Destabilizing	0.035	N	0.373	neutral	None	None	None	None	I
D/T	0.1782	likely_benign	0.1672	benign	-0.872	Destabilizing	0.081	N	0.419	neutral	None	None	None	None	I
D/V	0.1587	likely_benign	0.1581	benign	0.275	Stabilizing	0.211	N	0.573	neutral	N	0.512123715	None	None	I
D/W	0.6948	likely_pathogenic	0.7181	pathogenic	0.36	Stabilizing	0.935	D	0.609	neutral	None	None	None	None	I
D/Y	0.1112	likely_benign	0.1186	benign	0.403	Stabilizing	0.741	D	0.587	neutral	D	0.572310485	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.