TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9328	28207;28208;28209	chr2:178711254;178711253;178711252	chr2:179575981;179575980;179575979
N2AB	9011	27256;27257;27258	chr2:178711254;178711253;178711252	chr2:179575981;179575980;179575979
N2A	8084	24475;24476;24477	chr2:178711254;178711253;178711252	chr2:179575981;179575980;179575979
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-79
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.8988
• 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	rs1577830171	None	0.472	None	0.393	0.092	0.238096912614	gnomAD-4.0.0	1.5911E-06	None	None	None	None	I	None	0	2.28634E-05	None	0	0	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	0.0966	likely_benign	0.118	benign	-0.02	Destabilizing	0.309	N	0.387	neutral	None	None	None	None	I
E/C	0.7928	likely_pathogenic	0.8686	pathogenic	-0.196	Destabilizing	0.996	D	0.461	neutral	None	None	None	None	I
E/D	0.1246	likely_benign	0.154	benign	-0.347	Destabilizing	0.472	N	0.393	neutral	None	None	None	None	I
E/F	0.5124	ambiguous	0.6517	pathogenic	0.066	Stabilizing	0.984	D	0.47	neutral	None	None	None	None	I
E/G	0.1218	likely_benign	0.1679	benign	-0.165	Destabilizing	0.684	D	0.384	neutral	None	None	None	None	I
E/H	0.3159	likely_benign	0.3983	ambiguous	0.667	Stabilizing	0.953	D	0.383	neutral	None	None	None	None	I
E/I	0.2434	likely_benign	0.3159	benign	0.31	Stabilizing	0.953	D	0.481	neutral	None	None	None	None	I
E/K	0.0868	likely_benign	0.1148	benign	0.519	Stabilizing	0.309	N	0.368	neutral	None	None	None	None	I
E/L	0.2497	likely_benign	0.3256	benign	0.31	Stabilizing	0.742	D	0.529	neutral	None	None	None	None	I
E/M	0.3235	likely_benign	0.4035	ambiguous	0.057	Stabilizing	0.987	D	0.441	neutral	None	None	None	None	I
E/N	0.1925	likely_benign	0.2585	benign	0.096	Stabilizing	0.742	D	0.421	neutral	None	None	None	None	I
E/P	0.2663	likely_benign	0.3823	ambiguous	0.219	Stabilizing	0.009	N	0.192	neutral	None	None	None	None	I
E/Q	0.0944	likely_benign	0.1126	benign	0.135	Stabilizing	0.028	N	0.225	neutral	None	None	None	None	I
E/R	0.1562	likely_benign	0.2112	benign	0.789	Stabilizing	0.59	D	0.419	neutral	None	None	None	None	I
E/S	0.1124	likely_benign	0.1453	benign	-0.003	Destabilizing	0.045	N	0.115	neutral	None	None	None	None	I
E/T	0.1526	likely_benign	0.2011	benign	0.13	Stabilizing	0.59	D	0.42	neutral	None	None	None	None	I
E/V	0.1469	likely_benign	0.1805	benign	0.219	Stabilizing	0.684	D	0.499	neutral	None	None	None	None	I
E/W	0.7946	likely_pathogenic	0.8938	pathogenic	0.156	Stabilizing	0.996	D	0.532	neutral	None	None	None	None	I
E/Y	0.4087	ambiguous	0.5277	ambiguous	0.308	Stabilizing	0.953	D	0.454	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.