TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25292	76099;76100;76101	chr2:178570258;178570257;178570256	chr2:179434985;179434984;179434983
N2AB	23651	71176;71177;71178	chr2:178570258;178570257;178570256	chr2:179434985;179434984;179434983
N2A	22724	68395;68396;68397	chr2:178570258;178570257;178570256	chr2:179434985;179434984;179434983
N2B	16227	48904;48905;48906	chr2:178570258;178570257;178570256	chr2:179434985;179434984;179434983
Novex-1	16352	49279;49280;49281	chr2:178570258;178570257;178570256	chr2:179434985;179434984;179434983
Novex-2	16419	49480;49481;49482	chr2:178570258;178570257;178570256	chr2:179434985;179434984;179434983
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: Fn3-71
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.9528
• 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	rs1707677184	None	0.997	N	0.659	0.127	0.530060385853	gnomAD-4.0.0	1.59208E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02663E-05
E/Q	rs1015604651	None	0.999	N	0.689	0.228	0.438383285633	gnomAD-4.0.0	1.59211E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02682E-05

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	0.2016	likely_benign	0.2105	benign	-0.941	Destabilizing	0.997	D	0.752	deleterious	N	0.486933777	None	None	I
E/C	0.8195	likely_pathogenic	0.8301	pathogenic	-0.434	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/D	0.2264	likely_benign	0.2262	benign	-0.985	Destabilizing	0.997	D	0.659	prob.neutral	N	0.482249743	None	None	I
E/F	0.6736	likely_pathogenic	0.6994	pathogenic	-0.198	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	I
E/G	0.3522	ambiguous	0.3803	ambiguous	-1.318	Destabilizing	0.999	D	0.595	neutral	N	0.514939534	None	None	I
E/H	0.5587	ambiguous	0.5739	pathogenic	-0.308	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
E/I	0.2568	likely_benign	0.2615	benign	0.097	Stabilizing	0.999	D	0.744	deleterious	None	None	None	None	I
E/K	0.3177	likely_benign	0.3315	benign	-0.414	Destabilizing	0.997	D	0.723	deleterious	N	0.491693491	None	None	I
E/L	0.2898	likely_benign	0.3042	benign	0.097	Stabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	I
E/M	0.4033	ambiguous	0.4086	ambiguous	0.509	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
E/N	0.4231	ambiguous	0.4317	ambiguous	-1.024	Destabilizing	0.999	D	0.739	deleterious	None	None	None	None	I
E/P	0.6191	likely_pathogenic	0.7169	pathogenic	-0.228	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	I
E/Q	0.1788	likely_benign	0.1834	benign	-0.885	Destabilizing	0.999	D	0.689	prob.delet.	N	0.497194744	None	None	I
E/R	0.4604	ambiguous	0.4826	ambiguous	-0.066	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	I
E/S	0.3118	likely_benign	0.3214	benign	-1.341	Destabilizing	0.998	D	0.705	prob.delet.	None	None	None	None	I
E/T	0.2552	likely_benign	0.2554	benign	-1.017	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	I
E/V	0.1476	likely_benign	0.1498	benign	-0.228	Destabilizing	0.999	D	0.717	prob.delet.	N	0.491239418	None	None	I
E/W	0.9074	likely_pathogenic	0.9186	pathogenic	0.161	Stabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
E/Y	0.6549	likely_pathogenic	0.6785	pathogenic	0.106	Stabilizing	1.0	D	0.751	deleterious	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.