TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5681	17266;17267;17268	chr2:178731834;178731833;178731832	chr2:179596561;179596560;179596559
N2AB	5364	16315;16316;16317	chr2:178731834;178731833;178731832	chr2:179596561;179596560;179596559
N2A	4437	13534;13535;13536	chr2:178731834;178731833;178731832	chr2:179596561;179596560;179596559
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-40
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.9774
• 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
R/G	rs2080582630	None	0.684	N	0.44	0.172	0.311691414656	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/G	rs2080582630	None	0.684	N	0.44	0.172	0.311691414656	gnomAD-4.0.0	5.12417E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.57245E-06	0	0
R/S	None	None	0.684	N	0.458	0.258	0.0297737177859	gnomAD-4.0.0	1.59125E-06	None	None	None	None	I	None	0	0	None	0	2.773E-05	None	0	0	0	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
R/A	0.76	likely_pathogenic	0.6619	pathogenic	-0.193	Destabilizing	0.373	N	0.434	neutral	None	None	None	None	I
R/C	0.4973	ambiguous	0.4247	ambiguous	-0.523	Destabilizing	0.996	D	0.393	neutral	None	None	None	None	I
R/D	0.9074	likely_pathogenic	0.8503	pathogenic	-0.502	Destabilizing	0.009	N	0.315	neutral	None	None	None	None	I
R/E	0.717	likely_pathogenic	0.6175	pathogenic	-0.491	Destabilizing	0.373	N	0.404	neutral	None	None	None	None	I
R/F	0.8473	likely_pathogenic	0.7645	pathogenic	-0.569	Destabilizing	0.984	D	0.397	neutral	None	None	None	None	I
R/G	0.5292	ambiguous	0.4295	ambiguous	-0.261	Destabilizing	0.684	D	0.44	neutral	N	0.479831908	None	None	I
R/H	0.246	likely_benign	0.2134	benign	-0.711	Destabilizing	0.953	D	0.432	neutral	None	None	None	None	I
R/I	0.6121	likely_pathogenic	0.483	ambiguous	-0.061	Destabilizing	0.939	D	0.431	neutral	N	0.467213004	None	None	I
R/K	0.1305	likely_benign	0.1137	benign	-0.528	Destabilizing	0.001	N	0.157	neutral	N	0.458131271	None	None	I
R/L	0.5804	likely_pathogenic	0.4708	ambiguous	-0.061	Destabilizing	0.742	D	0.477	neutral	None	None	None	None	I
R/M	0.6134	likely_pathogenic	0.5003	ambiguous	-0.371	Destabilizing	0.984	D	0.432	neutral	None	None	None	None	I
R/N	0.8444	likely_pathogenic	0.759	pathogenic	-0.461	Destabilizing	0.742	D	0.418	neutral	None	None	None	None	I
R/P	0.674	likely_pathogenic	0.5838	pathogenic	-0.093	Destabilizing	0.953	D	0.461	neutral	None	None	None	None	I
R/Q	0.2014	likely_benign	0.1706	benign	-0.453	Destabilizing	0.742	D	0.435	neutral	None	None	None	None	I
R/S	0.8289	likely_pathogenic	0.7453	pathogenic	-0.551	Destabilizing	0.684	D	0.458	neutral	N	0.468230835	None	None	I
R/T	0.6862	likely_pathogenic	0.5585	ambiguous	-0.475	Destabilizing	0.684	D	0.481	neutral	N	0.474004801	None	None	I
R/V	0.7014	likely_pathogenic	0.5941	pathogenic	-0.093	Destabilizing	0.742	D	0.473	neutral	None	None	None	None	I
R/W	0.3638	ambiguous	0.3033	benign	-0.811	Destabilizing	0.996	D	0.43	neutral	None	None	None	None	I
R/Y	0.6907	likely_pathogenic	0.5753	pathogenic	-0.474	Destabilizing	0.984	D	0.417	neutral	None	None	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.