TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5080	15463;15464;15465	chr2:178734586;178734585;178734584	chr2:179599313;179599312;179599311
N2AB	4763	14512;14513;14514	chr2:178734586;178734585;178734584	chr2:179599313;179599312;179599311
N2A	3836	11731;11732;11733	chr2:178734586;178734585;178734584	chr2:179599313;179599312;179599311
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-34
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7605
• 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
T/I	rs755865502	0.2	0.966	N	0.363	0.312	0.485991781493	gnomAD-2.1.1	4.61E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.85E-06	0
T/I	rs755865502	0.2	0.966	N	0.363	0.312	0.485991781493	gnomAD-4.0.0	1.69801E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.0255E-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	0.0709	likely_benign	0.0679	benign	-0.891	Destabilizing	0.625	D	0.329	neutral	N	0.519020041	None	None	I
T/C	0.3766	ambiguous	0.3176	benign	-0.471	Destabilizing	0.998	D	0.378	neutral	None	None	None	None	I
T/D	0.2908	likely_benign	0.2566	benign	0.097	Stabilizing	0.016	N	0.135	neutral	None	None	None	None	I
T/E	0.1782	likely_benign	0.1749	benign	0.104	Stabilizing	0.029	N	0.113	neutral	None	None	None	None	I
T/F	0.1943	likely_benign	0.1828	benign	-0.885	Destabilizing	0.991	D	0.393	neutral	None	None	None	None	I
T/G	0.2045	likely_benign	0.1779	benign	-1.156	Destabilizing	0.842	D	0.4	neutral	None	None	None	None	I
T/H	0.1813	likely_benign	0.1583	benign	-1.344	Destabilizing	0.991	D	0.382	neutral	None	None	None	None	I
T/I	0.1303	likely_benign	0.1165	benign	-0.272	Destabilizing	0.966	D	0.363	neutral	N	0.510990293	None	None	I
T/K	0.1082	likely_benign	0.1051	benign	-0.648	Destabilizing	0.016	N	0.164	neutral	None	None	None	None	I
T/L	0.0813	likely_benign	0.076	benign	-0.272	Destabilizing	0.842	D	0.366	neutral	None	None	None	None	I
T/M	0.0724	likely_benign	0.0712	benign	-0.056	Destabilizing	0.998	D	0.353	neutral	None	None	None	None	I
T/N	0.0976	likely_benign	0.0864	benign	-0.525	Destabilizing	0.801	D	0.29	neutral	N	0.520258761	None	None	I
T/P	0.0759	likely_benign	0.0678	benign	-0.446	Destabilizing	0.891	D	0.393	neutral	N	0.441708405	None	None	I
T/Q	0.1408	likely_benign	0.1313	benign	-0.664	Destabilizing	0.842	D	0.403	neutral	None	None	None	None	I
T/R	0.1031	likely_benign	0.1004	benign	-0.449	Destabilizing	0.728	D	0.409	neutral	None	None	None	None	I
T/S	0.0987	likely_benign	0.0904	benign	-0.878	Destabilizing	0.625	D	0.337	neutral	N	0.5049077	None	None	I
T/V	0.1048	likely_benign	0.0979	benign	-0.446	Destabilizing	0.915	D	0.295	neutral	None	None	None	None	I
T/W	0.5269	ambiguous	0.4891	ambiguous	-0.785	Destabilizing	0.998	D	0.411	neutral	None	None	None	None	I
T/Y	0.219	likely_benign	0.1959	benign	-0.572	Destabilizing	0.991	D	0.393	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.