TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2712	8359;8360;8361	chr2:178770658;178770657;178770656	chr2:179635385;179635384;179635383
N2AB	2712	8359;8360;8361	chr2:178770658;178770657;178770656	chr2:179635385;179635384;179635383
N2A	2712	8359;8360;8361	chr2:178770658;178770657;178770656	chr2:179635385;179635384;179635383
N2B	2666	8221;8222;8223	chr2:178770658;178770657;178770656	chr2:179635385;179635384;179635383
Novex-1	2666	8221;8222;8223	chr2:178770658;178770657;178770656	chr2:179635385;179635384;179635383
Novex-2	2666	8221;8222;8223	chr2:178770658;178770657;178770656	chr2:179635385;179635384;179635383
Novex-3	2712	8359;8360;8361	chr2:178770658;178770657;178770656	chr2:179635385;179635384;179635383

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-17
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4809
• 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/S	rs886042774	None	0.999	N	0.521	0.261	0.33835085245	gnomAD-4.0.0	6.84641E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99326E-07	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	0.1709	likely_benign	0.1964	benign	-0.317	Destabilizing	0.999	D	0.503	neutral	N	0.500043073	None	None	N
T/C	0.7822	likely_pathogenic	0.8318	pathogenic	-0.341	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
T/D	0.6968	likely_pathogenic	0.7757	pathogenic	0.438	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/E	0.62	likely_pathogenic	0.7027	pathogenic	0.399	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/F	0.5249	ambiguous	0.5844	pathogenic	-0.637	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/G	0.401	ambiguous	0.4386	ambiguous	-0.497	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
T/H	0.4825	ambiguous	0.5481	ambiguous	-0.75	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
T/I	0.4153	ambiguous	0.4704	ambiguous	0.044	Stabilizing	1.0	D	0.737	prob.delet.	D	0.538746132	None	None	N
T/K	0.4689	ambiguous	0.5266	ambiguous	-0.338	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
T/L	0.2237	likely_benign	0.2427	benign	0.044	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
T/M	0.1437	likely_benign	0.1429	benign	-0.033	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
T/N	0.1973	likely_benign	0.2235	benign	-0.207	Destabilizing	1.0	D	0.693	prob.neutral	N	0.509109086	None	None	N
T/P	0.1377	likely_benign	0.1499	benign	-0.045	Destabilizing	1.0	D	0.729	prob.delet.	N	0.488347978	None	None	N
T/Q	0.4086	ambiguous	0.4585	ambiguous	-0.331	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/R	0.4509	ambiguous	0.5016	ambiguous	-0.164	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/S	0.2031	likely_benign	0.2302	benign	-0.447	Destabilizing	0.999	D	0.521	neutral	N	0.509221487	None	None	N
T/V	0.3139	likely_benign	0.363	ambiguous	-0.045	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
T/W	0.8392	likely_pathogenic	0.8701	pathogenic	-0.664	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
T/Y	0.52	ambiguous	0.5948	pathogenic	-0.369	Destabilizing	1.0	D	0.723	prob.delet.	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.