TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3885	11878;11879;11880	chr2:178741580;178741579;178741578	chr2:179606307;179606306;179606305
N2AB	3568	10927;10928;10929	chr2:178741580;178741579;178741578	chr2:179606307;179606306;179606305
N2A	None	None	chr2:None	chr2:None
N2B	3522	10789;10790;10791	chr2:178741580;178741579;178741578	chr2:179606307;179606306;179606305
Novex-1	3647	11164;11165;11166	chr2:178741580;178741579;178741578	chr2:179606307;179606306;179606305
Novex-2	3714	11365;11366;11367	chr2:178741580;178741579;178741578	chr2:179606307;179606306;179606305
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-27
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.493
• 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/Q	rs761154231	0.105	0.001	N	0.125	0.064	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/Q	rs761154231	0.105	0.001	N	0.125	0.064	None	gnomAD-4.0.0	1.36839E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7989E-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
E/A	0.1568	likely_benign	0.1443	benign	-0.486	Destabilizing	0.001	N	0.169	neutral	N	0.458044729	None	None	I
E/C	0.8399	likely_pathogenic	0.8089	pathogenic	-0.344	Destabilizing	0.883	D	0.299	neutral	None	None	None	None	I
E/D	0.1738	likely_benign	0.1684	benign	-0.426	Destabilizing	None	N	0.101	neutral	N	0.447951353	None	None	I
E/F	0.793	likely_pathogenic	0.7462	pathogenic	-0.198	Destabilizing	0.667	D	0.317	neutral	None	None	None	None	I
E/G	0.1528	likely_benign	0.1283	benign	-0.696	Destabilizing	None	N	0.172	neutral	N	0.460847977	None	None	I
E/H	0.4956	ambiguous	0.4804	ambiguous	0.199	Stabilizing	0.497	N	0.267	neutral	None	None	None	None	I
E/I	0.4432	ambiguous	0.4159	ambiguous	0.042	Stabilizing	0.497	N	0.357	neutral	None	None	None	None	I
E/K	0.1352	likely_benign	0.1284	benign	0.103	Stabilizing	0.042	N	0.249	neutral	N	0.444104959	None	None	I
E/L	0.4552	ambiguous	0.4302	ambiguous	0.042	Stabilizing	0.124	N	0.381	neutral	None	None	None	None	I
E/M	0.4897	ambiguous	0.4685	ambiguous	0.018	Stabilizing	0.667	D	0.293	neutral	None	None	None	None	I
E/N	0.3301	likely_benign	0.3117	benign	-0.331	Destabilizing	0.001	N	0.219	neutral	None	None	None	None	I
E/P	0.5678	likely_pathogenic	0.5798	pathogenic	-0.114	Destabilizing	0.364	N	0.367	neutral	None	None	None	None	I
E/Q	0.145	likely_benign	0.1451	benign	-0.273	Destabilizing	0.001	N	0.125	neutral	N	0.461248151	None	None	I
E/R	0.2271	likely_benign	0.2104	benign	0.466	Stabilizing	0.124	N	0.274	neutral	None	None	None	None	I
E/S	0.2244	likely_benign	0.2087	benign	-0.494	Destabilizing	0.055	N	0.277	neutral	None	None	None	None	I
E/T	0.2605	likely_benign	0.2358	benign	-0.316	Destabilizing	0.22	N	0.331	neutral	None	None	None	None	I
E/V	0.2759	likely_benign	0.2561	benign	-0.114	Destabilizing	0.096	N	0.387	neutral	D	0.524047226	None	None	I
E/W	0.8476	likely_pathogenic	0.8172	pathogenic	0.006	Stabilizing	0.958	D	0.345	neutral	None	None	None	None	I
E/Y	0.6869	likely_pathogenic	0.6415	pathogenic	0.047	Stabilizing	0.667	D	0.302	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.