TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7547	22864;22865;22866	chr2:178722024;178722023;178722022	chr2:179586751;179586750;179586749
N2AB	7230	21913;21914;21915	chr2:178722024;178722023;178722022	chr2:179586751;179586750;179586749
N2A	6303	19132;19133;19134	chr2:178722024;178722023;178722022	chr2:179586751;179586750;179586749
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-60
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.3788
• 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
T/S	rs1437517914	-1.179	0.573	N	0.519	0.17	0.210429274316	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
T/S	rs1437517914	-1.179	0.573	N	0.519	0.17	0.210429274316	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1437517914	-1.179	0.573	N	0.519	0.17	0.210429274316	gnomAD-4.0.0	2.56298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78829E-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
T/A	0.0897	likely_benign	0.0916	benign	-0.833	Destabilizing	0.008	N	0.322	neutral	N	0.512433556	None	None	N
T/C	0.4419	ambiguous	0.4623	ambiguous	-0.493	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
T/D	0.5748	likely_pathogenic	0.5746	pathogenic	-0.359	Destabilizing	0.987	D	0.568	neutral	None	None	None	None	N
T/E	0.4664	ambiguous	0.467	ambiguous	-0.325	Destabilizing	0.973	D	0.526	neutral	None	None	None	None	N
T/F	0.1723	likely_benign	0.1813	benign	-0.762	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
T/G	0.2794	likely_benign	0.2976	benign	-1.132	Destabilizing	0.979	D	0.578	neutral	None	None	None	None	N
T/H	0.2407	likely_benign	0.2373	benign	-1.375	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
T/I	0.116	likely_benign	0.1172	benign	-0.116	Destabilizing	0.993	D	0.599	neutral	N	0.489308767	None	None	N
T/K	0.2642	likely_benign	0.2584	benign	-0.766	Destabilizing	0.406	N	0.403	neutral	None	None	None	None	N
T/L	0.0905	likely_benign	0.0981	benign	-0.116	Destabilizing	0.981	D	0.517	neutral	None	None	None	None	N
T/M	0.0899	likely_benign	0.0923	benign	0.076	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	N
T/N	0.1445	likely_benign	0.1479	benign	-0.783	Destabilizing	0.983	D	0.51	neutral	N	0.520938396	None	None	N
T/P	0.5981	likely_pathogenic	0.6456	pathogenic	-0.322	Destabilizing	0.983	D	0.599	neutral	N	0.510953516	None	None	N
T/Q	0.2558	likely_benign	0.25	benign	-0.862	Destabilizing	0.988	D	0.6	neutral	None	None	None	None	N
T/R	0.2011	likely_benign	0.2002	benign	-0.592	Destabilizing	0.809	D	0.394	neutral	None	None	None	None	N
T/S	0.0975	likely_benign	0.1027	benign	-1.04	Destabilizing	0.573	D	0.519	neutral	N	0.416037585	None	None	N
T/V	0.1085	likely_benign	0.111	benign	-0.322	Destabilizing	0.948	D	0.485	neutral	None	None	None	None	N
T/W	0.5559	ambiguous	0.5659	pathogenic	-0.735	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/Y	0.2694	likely_benign	0.2741	benign	-0.498	Destabilizing	1.0	D	0.68	prob.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.