TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2801	8626;8627;8628	chr2:178770300;178770299;178770298	chr2:179635027;179635026;179635025
N2AB	2801	8626;8627;8628	chr2:178770300;178770299;178770298	chr2:179635027;179635026;179635025
N2A	2801	8626;8627;8628	chr2:178770300;178770299;178770298	chr2:179635027;179635026;179635025
N2B	2755	8488;8489;8490	chr2:178770300;178770299;178770298	chr2:179635027;179635026;179635025
Novex-1	2755	8488;8489;8490	chr2:178770300;178770299;178770298	chr2:179635027;179635026;179635025
Novex-2	2755	8488;8489;8490	chr2:178770300;178770299;178770298	chr2:179635027;179635026;179635025
Novex-3	2801	8626;8627;8628	chr2:178770300;178770299;178770298	chr2:179635027;179635026;179635025

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-18
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1514
• 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
P/Q	None	None	0.966	D	0.739	0.397	0.356484672536	gnomAD-4.0.0	1.59049E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
P/A	0.7982	likely_pathogenic	0.8654	pathogenic	-1.975	Destabilizing	0.005	N	0.355	neutral	N	0.498621765	None	None	N
P/C	0.9843	likely_pathogenic	0.9904	pathogenic	-1.201	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
P/D	0.9995	likely_pathogenic	0.9996	pathogenic	-2.437	Highly Destabilizing	0.915	D	0.703	prob.neutral	None	None	None	None	N
P/E	0.9982	likely_pathogenic	0.9984	pathogenic	-2.289	Highly Destabilizing	0.842	D	0.653	neutral	None	None	None	None	N
P/F	0.9974	likely_pathogenic	0.9983	pathogenic	-1.243	Destabilizing	0.949	D	0.767	deleterious	None	None	None	None	N
P/G	0.9882	likely_pathogenic	0.9924	pathogenic	-2.442	Highly Destabilizing	0.728	D	0.636	neutral	None	None	None	None	N
P/H	0.998	likely_pathogenic	0.9984	pathogenic	-2.168	Highly Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
P/I	0.913	likely_pathogenic	0.932	pathogenic	-0.704	Destabilizing	0.067	N	0.584	neutral	None	None	None	None	N
P/K	0.9991	likely_pathogenic	0.9993	pathogenic	-1.733	Destabilizing	0.842	D	0.645	neutral	None	None	None	None	N
P/L	0.6502	likely_pathogenic	0.7473	pathogenic	-0.704	Destabilizing	0.012	N	0.493	neutral	N	0.445085016	None	None	N
P/M	0.9352	likely_pathogenic	0.9602	pathogenic	-0.478	Destabilizing	0.949	D	0.696	prob.neutral	None	None	None	None	N
P/N	0.9984	likely_pathogenic	0.9989	pathogenic	-1.799	Destabilizing	0.974	D	0.715	prob.delet.	None	None	None	None	N
P/Q	0.995	likely_pathogenic	0.9962	pathogenic	-1.77	Destabilizing	0.966	D	0.739	prob.delet.	D	0.605008006	None	None	N
P/R	0.9976	likely_pathogenic	0.9978	pathogenic	-1.39	Destabilizing	0.966	D	0.719	prob.delet.	D	0.605008006	None	None	N
P/S	0.9898	likely_pathogenic	0.9935	pathogenic	-2.349	Highly Destabilizing	0.669	D	0.607	neutral	D	0.603708585	None	None	N
P/T	0.9623	likely_pathogenic	0.9759	pathogenic	-2.082	Highly Destabilizing	0.051	N	0.376	neutral	D	0.523610775	None	None	N
P/V	0.8756	likely_pathogenic	0.9096	pathogenic	-1.099	Destabilizing	0.525	D	0.562	neutral	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.733	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
P/Y	0.9992	likely_pathogenic	0.9994	pathogenic	-1.369	Destabilizing	0.991	D	0.763	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.