TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3964	12115;12116;12117	chr2:178741343;178741342;178741341	chr2:179606070;179606069;179606068
N2AB	3647	11164;11165;11166	chr2:178741343;178741342;178741341	chr2:179606070;179606069;179606068
N2A	None	None	chr2:None	chr2:None
N2B	3601	11026;11027;11028	chr2:178741343;178741342;178741341	chr2:179606070;179606069;179606068
Novex-1	3726	11401;11402;11403	chr2:178741343;178741342;178741341	chr2:179606070;179606069;179606068
Novex-2	3793	11602;11603;11604	chr2:178741343;178741342;178741341	chr2:179606070;179606069;179606068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-28
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.8554
• 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
E/D	rs1410220479	-0.021	None	N	0.175	0.084	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/D	rs1410220479	-0.021	None	N	0.175	0.084	None	gnomAD-4.0.0	2.73669E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59775E-06	0	0
E/Q	None	None	0.175	N	0.438	0.1	None	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
E/V	rs756497264	0.431	0.001	N	0.402	0.178	None	gnomAD-4.0.0	1.59106E-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
E/A	0.2194	likely_benign	0.2081	benign	-0.066	Destabilizing	0.042	N	0.453	neutral	N	0.499194585	None	None	I
E/C	0.8091	likely_pathogenic	0.8015	pathogenic	-0.153	Destabilizing	0.883	D	0.497	neutral	None	None	None	None	I
E/D	0.1559	likely_benign	0.1516	benign	-0.236	Destabilizing	None	N	0.175	neutral	N	0.4654025	None	None	I
E/F	0.6125	likely_pathogenic	0.5948	pathogenic	-0.086	Destabilizing	0.497	N	0.519	neutral	None	None	None	None	I
E/G	0.2704	likely_benign	0.2302	benign	-0.195	Destabilizing	0.042	N	0.566	neutral	D	0.569470566	None	None	I
E/H	0.4246	ambiguous	0.4284	ambiguous	0.485	Stabilizing	0.667	D	0.431	neutral	None	None	None	None	I
E/I	0.2947	likely_benign	0.2935	benign	0.217	Stabilizing	0.046	N	0.57	neutral	None	None	None	None	I
E/K	0.1395	likely_benign	0.1228	benign	0.41	Stabilizing	0.001	N	0.258	neutral	N	0.497472054	None	None	I
E/L	0.4012	ambiguous	0.3927	ambiguous	0.217	Stabilizing	0.124	N	0.575	neutral	None	None	None	None	I
E/M	0.3919	ambiguous	0.3839	ambiguous	0.026	Stabilizing	0.667	D	0.518	neutral	None	None	None	None	I
E/N	0.2294	likely_benign	0.2296	benign	0.189	Stabilizing	0.001	N	0.259	neutral	None	None	None	None	I
E/P	0.9258	likely_pathogenic	0.8836	pathogenic	0.141	Stabilizing	0.364	N	0.501	neutral	None	None	None	None	I
E/Q	0.141	likely_benign	0.1443	benign	0.198	Stabilizing	0.175	N	0.438	neutral	N	0.509162563	None	None	I
E/R	0.2687	likely_benign	0.245	benign	0.656	Stabilizing	0.124	N	0.431	neutral	None	None	None	None	I
E/S	0.2103	likely_benign	0.2033	benign	0.026	Stabilizing	0.001	N	0.239	neutral	None	None	None	None	I
E/T	0.245	likely_benign	0.236	benign	0.135	Stabilizing	0.004	N	0.287	neutral	None	None	None	None	I
E/V	0.2011	likely_benign	0.1965	benign	0.141	Stabilizing	0.001	N	0.402	neutral	N	0.503770688	None	None	I
E/W	0.8708	likely_pathogenic	0.8518	pathogenic	-0.025	Destabilizing	0.958	D	0.523	neutral	None	None	None	None	I
E/Y	0.4965	ambiguous	0.4789	ambiguous	0.142	Stabilizing	0.667	D	0.521	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.