TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2762	8509;8510;8511	chr2:178770508;178770507;178770506	chr2:179635235;179635234;179635233
N2AB	2762	8509;8510;8511	chr2:178770508;178770507;178770506	chr2:179635235;179635234;179635233
N2A	2762	8509;8510;8511	chr2:178770508;178770507;178770506	chr2:179635235;179635234;179635233
N2B	2716	8371;8372;8373	chr2:178770508;178770507;178770506	chr2:179635235;179635234;179635233
Novex-1	2716	8371;8372;8373	chr2:178770508;178770507;178770506	chr2:179635235;179635234;179635233
Novex-2	2716	8371;8372;8373	chr2:178770508;178770507;178770506	chr2:179635235;179635234;179635233
Novex-3	2762	8509;8510;8511	chr2:178770508;178770507;178770506	chr2:179635235;179635234;179635233

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-17
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0478
• 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
Y/C	rs1553995474	None	0.993	N	0.695	0.753	0.728573421076	gnomAD-4.0.0	3.18101E-06	None	None	None	None	N	None	5.65163E-05	0	None	0	0	None	0	0	2.85649E-06	0	0
Y/H	None	None	0.001	N	0.312	0.389	0.321951552304	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.5927	likely_pathogenic	0.7252	pathogenic	-2.521	Highly Destabilizing	0.495	N	0.677	prob.neutral	None	None	None	None	N
Y/C	0.1186	likely_benign	0.1576	benign	-1.771	Destabilizing	0.993	D	0.695	prob.neutral	N	0.512062918	None	None	N
Y/D	0.7159	likely_pathogenic	0.871	pathogenic	-2.603	Highly Destabilizing	0.642	D	0.711	prob.delet.	N	0.510450919	None	None	N
Y/E	0.8243	likely_pathogenic	0.9208	pathogenic	-2.36	Highly Destabilizing	0.329	N	0.69	prob.neutral	None	None	None	None	N
Y/F	0.1325	likely_benign	0.1453	benign	-0.764	Destabilizing	0.784	D	0.631	neutral	N	0.516142335	None	None	N
Y/G	0.6569	likely_pathogenic	0.7868	pathogenic	-2.98	Highly Destabilizing	0.495	N	0.689	prob.neutral	None	None	None	None	N
Y/H	0.0984	likely_benign	0.153	benign	-1.894	Destabilizing	0.001	N	0.312	neutral	N	0.357747074	None	None	N
Y/I	0.5766	likely_pathogenic	0.7074	pathogenic	-1.015	Destabilizing	0.828	D	0.701	prob.neutral	None	None	None	None	N
Y/K	0.7837	likely_pathogenic	0.8893	pathogenic	-1.855	Destabilizing	0.329	N	0.675	prob.neutral	None	None	None	None	N
Y/L	0.5186	ambiguous	0.6269	pathogenic	-1.015	Destabilizing	0.495	N	0.669	neutral	None	None	None	None	N
Y/M	0.7692	likely_pathogenic	0.8342	pathogenic	-1.077	Destabilizing	0.981	D	0.693	prob.neutral	None	None	None	None	N
Y/N	0.3063	likely_benign	0.4653	ambiguous	-2.678	Highly Destabilizing	0.642	D	0.691	prob.neutral	N	0.510982371	None	None	N
Y/P	0.9494	likely_pathogenic	0.9791	pathogenic	-1.531	Destabilizing	0.936	D	0.739	prob.delet.	None	None	None	None	N
Y/Q	0.5065	ambiguous	0.6718	pathogenic	-2.292	Highly Destabilizing	0.037	N	0.503	neutral	None	None	None	None	N
Y/R	0.472	ambiguous	0.6424	pathogenic	-1.942	Destabilizing	0.704	D	0.701	prob.neutral	None	None	None	None	N
Y/S	0.2773	likely_benign	0.412	ambiguous	-3.131	Highly Destabilizing	0.425	N	0.673	neutral	N	0.510836456	None	None	N
Y/T	0.5396	ambiguous	0.6809	pathogenic	-2.745	Highly Destabilizing	0.828	D	0.702	prob.neutral	None	None	None	None	N
Y/V	0.4597	ambiguous	0.5769	pathogenic	-1.531	Destabilizing	0.828	D	0.704	prob.neutral	None	None	None	None	N
Y/W	0.4771	ambiguous	0.5157	ambiguous	-0.028	Destabilizing	0.981	D	0.671	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.