TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29925	89998;89999;90000	chr2:178553127;178553126;178553125	chr2:179417854;179417853;179417852
N2AB	28284	85075;85076;85077	chr2:178553127;178553126;178553125	chr2:179417854;179417853;179417852
N2A	27357	82294;82295;82296	chr2:178553127;178553126;178553125	chr2:179417854;179417853;179417852
N2B	20860	62803;62804;62805	chr2:178553127;178553126;178553125	chr2:179417854;179417853;179417852
Novex-1	20985	63178;63179;63180	chr2:178553127;178553126;178553125	chr2:179417854;179417853;179417852
Novex-2	21052	63379;63380;63381	chr2:178553127;178553126;178553125	chr2:179417854;179417853;179417852
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-147
• Domain position: 84
• Structural Position: 171
• Q(SASA): 0.3679
• 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	rs780250655	-0.735	0.001	N	0.171	0.111	0.301455362545	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
T/S	rs780250655	-0.735	0.001	N	0.171	0.111	0.301455362545	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
T/A	0.0899	likely_benign	0.0814	benign	-0.794	Destabilizing	0.09	N	0.455	neutral	D	0.526440216	None	None	N
T/C	0.4943	ambiguous	0.4031	ambiguous	-0.451	Destabilizing	0.944	D	0.565	neutral	None	None	None	None	N
T/D	0.6009	likely_pathogenic	0.4838	ambiguous	0.467	Stabilizing	0.388	N	0.566	neutral	None	None	None	None	N
T/E	0.4473	ambiguous	0.3592	ambiguous	0.437	Stabilizing	0.241	N	0.564	neutral	None	None	None	None	N
T/F	0.2034	likely_benign	0.1609	benign	-1.09	Destabilizing	0.002	N	0.374	neutral	None	None	None	None	N
T/G	0.3559	ambiguous	0.2902	benign	-0.985	Destabilizing	0.241	N	0.621	neutral	None	None	None	None	N
T/H	0.3027	likely_benign	0.2421	benign	-1.258	Destabilizing	0.944	D	0.637	neutral	None	None	None	None	N
T/I	0.175	likely_benign	0.1514	benign	-0.39	Destabilizing	0.193	N	0.581	neutral	D	0.535022414	None	None	N
T/K	0.3891	ambiguous	0.3075	benign	-0.383	Destabilizing	0.241	N	0.571	neutral	None	None	None	None	N
T/L	0.1313	likely_benign	0.1077	benign	-0.39	Destabilizing	0.116	N	0.523	neutral	None	None	None	None	N
T/M	0.1002	likely_benign	0.0917	benign	-0.119	Destabilizing	0.818	D	0.583	neutral	None	None	None	None	N
T/N	0.1841	likely_benign	0.1477	benign	-0.246	Destabilizing	0.193	N	0.539	neutral	N	0.501640559	None	None	N
T/P	0.1971	likely_benign	0.1866	benign	-0.494	Destabilizing	0.773	D	0.625	neutral	N	0.490140236	None	None	N
T/Q	0.3181	likely_benign	0.2627	benign	-0.442	Destabilizing	0.69	D	0.611	neutral	None	None	None	None	N
T/R	0.3081	likely_benign	0.2317	benign	-0.199	Destabilizing	0.69	D	0.622	neutral	None	None	None	None	N
T/S	0.1266	likely_benign	0.1095	benign	-0.619	Destabilizing	0.001	N	0.171	neutral	N	0.456366842	None	None	N
T/V	0.125	likely_benign	0.1111	benign	-0.494	Destabilizing	0.388	N	0.498	neutral	None	None	None	None	N
T/W	0.5808	likely_pathogenic	0.4968	ambiguous	-0.975	Destabilizing	0.981	D	0.632	neutral	None	None	None	None	N
T/Y	0.2623	likely_benign	0.2066	benign	-0.73	Destabilizing	0.527	D	0.675	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.