TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33142	99649;99650;99651	chr2:178537783;178537782;178537781	chr2:179402510;179402509;179402508
N2AB	31501	94726;94727;94728	chr2:178537783;178537782;178537781	chr2:179402510;179402509;179402508
N2A	30574	91945;91946;91947	chr2:178537783;178537782;178537781	chr2:179402510;179402509;179402508
N2B	24077	72454;72455;72456	chr2:178537783;178537782;178537781	chr2:179402510;179402509;179402508
Novex-1	24202	72829;72830;72831	chr2:178537783;178537782;178537781	chr2:179402510;179402509;179402508
Novex-2	24269	73030;73031;73032	chr2:178537783;178537782;178537781	chr2:179402510;179402509;179402508
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-156
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.581
• 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
I/T	rs1338367198	None	0.01	N	0.367	0.136	0.601870671465	gnomAD-4.0.0	1.59137E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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
I/A	0.1762	likely_benign	0.2956	benign	-0.659	Destabilizing	None	N	0.181	neutral	None	None	None	None	I
I/C	0.5493	ambiguous	0.6594	pathogenic	-0.681	Destabilizing	0.704	D	0.33	neutral	None	None	None	None	I
I/D	0.508	ambiguous	0.6774	pathogenic	-0.312	Destabilizing	0.043	N	0.359	neutral	None	None	None	None	I
I/E	0.3631	ambiguous	0.4986	ambiguous	-0.372	Destabilizing	0.061	N	0.382	neutral	None	None	None	None	I
I/F	0.1206	likely_benign	0.1756	benign	-0.581	Destabilizing	0.11	N	0.329	neutral	None	None	None	None	I
I/G	0.3206	likely_benign	0.526	ambiguous	-0.839	Destabilizing	0.043	N	0.391	neutral	None	None	None	None	I
I/H	0.2942	likely_benign	0.4056	ambiguous	-0.049	Destabilizing	0.497	N	0.321	neutral	None	None	None	None	I
I/K	0.2201	likely_benign	0.2986	benign	-0.419	Destabilizing	0.002	N	0.373	neutral	N	0.448726007	None	None	I
I/L	0.081	likely_benign	0.1045	benign	-0.289	Destabilizing	None	N	0.207	neutral	N	0.460849942	None	None	I
I/M	0.0815	likely_benign	0.1088	benign	-0.521	Destabilizing	0.027	N	0.351	neutral	D	0.522245118	None	None	I
I/N	0.1423	likely_benign	0.2132	benign	-0.287	Destabilizing	0.001	N	0.329	neutral	None	None	None	None	I
I/P	0.4051	ambiguous	0.5553	ambiguous	-0.381	Destabilizing	0.387	N	0.356	neutral	None	None	None	None	I
I/Q	0.1974	likely_benign	0.2705	benign	-0.454	Destabilizing	0.208	N	0.351	neutral	None	None	None	None	I
I/R	0.1815	likely_benign	0.2349	benign	0.097	Stabilizing	0.159	N	0.355	neutral	N	0.471949583	None	None	I
I/S	0.139	likely_benign	0.2121	benign	-0.72	Destabilizing	0.043	N	0.377	neutral	None	None	None	None	I
I/T	0.1053	likely_benign	0.1746	benign	-0.668	Destabilizing	0.01	N	0.367	neutral	N	0.461521946	None	None	I
I/V	0.0664	likely_benign	0.0809	benign	-0.381	Destabilizing	None	N	0.189	neutral	N	0.47529932	None	None	I
I/W	0.6778	likely_pathogenic	0.7759	pathogenic	-0.616	Destabilizing	0.915	D	0.385	neutral	None	None	None	None	I
I/Y	0.3859	ambiguous	0.46	ambiguous	-0.374	Destabilizing	0.029	N	0.346	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.