TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7575	22948;22949;22950	chr2:178721940;178721939;178721938	chr2:179586667;179586666;179586665
N2AB	7258	21997;21998;21999	chr2:178721940;178721939;178721938	chr2:179586667;179586666;179586665
N2A	6331	19216;19217;19218	chr2:178721940;178721939;178721938	chr2:179586667;179586666;179586665
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-60
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.2597
• 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
L/P	None	None	0.999	N	0.719	0.487	0.832360729247	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
L/V	rs774759859	-1.238	0.597	N	0.515	0.256	0.566774491594	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	0	None	0	1.53657E-04	None	0	None	0	7.82E-06	0
L/V	rs774759859	-1.238	0.597	N	0.515	0.256	0.566774491594	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	3.861E-04	None	0	0	1.47E-05	0	0
L/V	rs774759859	-1.238	0.597	N	0.515	0.256	0.566774491594	gnomAD-4.0.0	7.68898E-06	None	None	None	None	N	None	0	0	None	0	9.69838E-05	None	0	0	4.78794E-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
L/A	0.3977	ambiguous	0.4294	ambiguous	-1.257	Destabilizing	0.99	D	0.527	neutral	None	None	None	None	N
L/C	0.7449	likely_pathogenic	0.7522	pathogenic	-0.887	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
L/D	0.8473	likely_pathogenic	0.8551	pathogenic	-0.274	Destabilizing	0.994	D	0.661	neutral	None	None	None	None	N
L/E	0.554	ambiguous	0.5825	pathogenic	-0.308	Destabilizing	0.992	D	0.628	neutral	None	None	None	None	N
L/F	0.1781	likely_benign	0.1988	benign	-0.941	Destabilizing	0.991	D	0.546	neutral	N	0.50229392	None	None	N
L/G	0.6586	likely_pathogenic	0.6913	pathogenic	-1.516	Destabilizing	0.997	D	0.635	neutral	None	None	None	None	N
L/H	0.3016	likely_benign	0.3384	benign	-0.627	Destabilizing	0.999	D	0.708	prob.delet.	N	0.501677844	None	None	N
L/I	0.1139	likely_benign	0.1204	benign	-0.655	Destabilizing	0.53	D	0.477	neutral	N	0.509835968	None	None	N
L/K	0.4027	ambiguous	0.4254	ambiguous	-0.607	Destabilizing	0.599	D	0.597	neutral	None	None	None	None	N
L/M	0.1427	likely_benign	0.1525	benign	-0.544	Destabilizing	0.714	D	0.379	neutral	None	None	None	None	N
L/N	0.4695	ambiguous	0.4817	ambiguous	-0.41	Destabilizing	0.759	D	0.421	neutral	None	None	None	None	N
L/P	0.5963	likely_pathogenic	0.6305	pathogenic	-0.822	Destabilizing	0.999	D	0.719	prob.delet.	N	0.498002821	None	None	N
L/Q	0.1734	likely_benign	0.1998	benign	-0.629	Destabilizing	0.791	D	0.447	neutral	None	None	None	None	N
L/R	0.2783	likely_benign	0.3346	benign	-0.042	Destabilizing	0.991	D	0.666	neutral	N	0.454403973	None	None	N
L/S	0.3597	ambiguous	0.3909	ambiguous	-1.08	Destabilizing	0.99	D	0.59	neutral	None	None	None	None	N
L/T	0.299	likely_benign	0.3305	benign	-0.999	Destabilizing	0.968	D	0.525	neutral	None	None	None	None	N
L/V	0.1222	likely_benign	0.1363	benign	-0.822	Destabilizing	0.597	D	0.515	neutral	N	0.511009404	None	None	N
L/W	0.3389	likely_benign	0.3785	ambiguous	-0.907	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
L/Y	0.4698	ambiguous	0.5095	ambiguous	-0.675	Destabilizing	0.99	D	0.633	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.