TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8402	25429;25430;25431	chr2:178717670;178717669;178717668	chr2:179582397;179582396;179582395
N2AB	8085	24478;24479;24480	chr2:178717670;178717669;178717668	chr2:179582397;179582396;179582395
N2A	7158	21697;21698;21699	chr2:178717670;178717669;178717668	chr2:179582397;179582396;179582395
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-69
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.7239
• Predicted PPI site: I

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
D/G	rs954211095	None	0.861	N	0.378	0.209	0.293502639404	gnomAD-4.0.0	1.59208E-06	None	None	None	None	I	None	0	2.2877E-05	None	0	0	None	0	0	0	0	0
D/N	None	None	0.111	N	0.225	0.178	0.247322355667	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
D/A	0.3336	likely_benign	0.4035	ambiguous	-0.261	Destabilizing	0.811	D	0.391	neutral	N	0.463735532	None	None	I
D/C	0.9032	likely_pathogenic	0.9312	pathogenic	0.148	Stabilizing	0.998	D	0.471	neutral	None	None	None	None	I
D/E	0.2769	likely_benign	0.3224	benign	-0.303	Destabilizing	0.03	N	0.243	neutral	N	0.463252742	None	None	I
D/F	0.891	likely_pathogenic	0.9214	pathogenic	-0.318	Destabilizing	1.0	D	0.441	neutral	None	None	None	None	I
D/G	0.2595	likely_benign	0.3142	benign	-0.449	Destabilizing	0.861	D	0.378	neutral	N	0.510027969	None	None	I
D/H	0.6007	likely_pathogenic	0.6838	pathogenic	-0.249	Destabilizing	0.995	D	0.355	neutral	D	0.527074934	None	None	I
D/I	0.7601	likely_pathogenic	0.8161	pathogenic	0.18	Stabilizing	0.999	D	0.453	neutral	None	None	None	None	I
D/K	0.6548	likely_pathogenic	0.7274	pathogenic	0.328	Stabilizing	0.99	D	0.376	neutral	None	None	None	None	I
D/L	0.7495	likely_pathogenic	0.8023	pathogenic	0.18	Stabilizing	0.999	D	0.431	neutral	None	None	None	None	I
D/M	0.8723	likely_pathogenic	0.9044	pathogenic	0.383	Stabilizing	1.0	D	0.449	neutral	None	None	None	None	I
D/N	0.1683	likely_benign	0.194	benign	0.103	Stabilizing	0.111	N	0.225	neutral	N	0.496405311	None	None	I
D/P	0.7054	likely_pathogenic	0.7687	pathogenic	0.055	Stabilizing	0.933	D	0.36	neutral	None	None	None	None	I
D/Q	0.6164	likely_pathogenic	0.6912	pathogenic	0.126	Stabilizing	0.992	D	0.303	neutral	None	None	None	None	I
D/R	0.6875	likely_pathogenic	0.7683	pathogenic	0.413	Stabilizing	0.997	D	0.421	neutral	None	None	None	None	I
D/S	0.2568	likely_benign	0.3109	benign	-0.003	Destabilizing	0.311	N	0.164	neutral	None	None	None	None	I
D/T	0.4824	ambiguous	0.5619	ambiguous	0.139	Stabilizing	0.86	D	0.384	neutral	None	None	None	None	I
D/V	0.5105	ambiguous	0.5908	pathogenic	0.055	Stabilizing	0.989	D	0.427	neutral	D	0.526554859	None	None	I
D/W	0.9602	likely_pathogenic	0.9723	pathogenic	-0.229	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	I
D/Y	0.4925	ambiguous	0.5709	pathogenic	-0.094	Destabilizing	0.999	D	0.442	neutral	N	0.489922745	None	None	I

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.