TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25841	77746;77747;77748	chr2:178568611;178568610;178568609	chr2:179433338;179433337;179433336
N2AB	24200	72823;72824;72825	chr2:178568611;178568610;178568609	chr2:179433338;179433337;179433336
N2A	23273	70042;70043;70044	chr2:178568611;178568610;178568609	chr2:179433338;179433337;179433336
N2B	16776	50551;50552;50553	chr2:178568611;178568610;178568609	chr2:179433338;179433337;179433336
Novex-1	16901	50926;50927;50928	chr2:178568611;178568610;178568609	chr2:179433338;179433337;179433336
Novex-2	16968	51127;51128;51129	chr2:178568611;178568610;178568609	chr2:179433338;179433337;179433336
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-136
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.4315
• 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/I	None	None	1.0	N	0.717	0.445	0.412328234245	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.6249	likely_pathogenic	0.5941	pathogenic	-0.321	Destabilizing	0.999	D	0.516	neutral	N	0.461919858	None	None	N
T/C	0.9489	likely_pathogenic	0.9484	pathogenic	-0.201	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
T/D	0.7691	likely_pathogenic	0.7574	pathogenic	0.089	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/E	0.9077	likely_pathogenic	0.898	pathogenic	0.011	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
T/F	0.9457	likely_pathogenic	0.9361	pathogenic	-0.802	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/G	0.6539	likely_pathogenic	0.6468	pathogenic	-0.454	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
T/H	0.8354	likely_pathogenic	0.8338	pathogenic	-0.763	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/I	0.9448	likely_pathogenic	0.933	pathogenic	-0.091	Destabilizing	1.0	D	0.717	prob.delet.	N	0.484178396	None	None	N
T/K	0.847	likely_pathogenic	0.843	pathogenic	-0.384	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
T/L	0.6947	likely_pathogenic	0.6533	pathogenic	-0.091	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
T/M	0.4461	ambiguous	0.4206	ambiguous	0.088	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/N	0.3796	ambiguous	0.3795	ambiguous	-0.129	Destabilizing	1.0	D	0.721	prob.delet.	N	0.498361741	None	None	N
T/P	0.8637	likely_pathogenic	0.8441	pathogenic	-0.139	Destabilizing	1.0	D	0.708	prob.delet.	N	0.462680327	None	None	N
T/Q	0.8351	likely_pathogenic	0.8236	pathogenic	-0.369	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
T/R	0.8633	likely_pathogenic	0.8557	pathogenic	-0.099	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
T/S	0.3478	ambiguous	0.3396	benign	-0.326	Destabilizing	0.999	D	0.518	neutral	N	0.469825558	None	None	N
T/V	0.8603	likely_pathogenic	0.8338	pathogenic	-0.139	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
T/W	0.9828	likely_pathogenic	0.9806	pathogenic	-0.819	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
T/Y	0.922	likely_pathogenic	0.9165	pathogenic	-0.537	Destabilizing	1.0	D	0.743	deleterious	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.