TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8255	24988;24989;24990	chr2:178718343;178718342;178718341	chr2:179583070;179583069;179583068
N2AB	7938	24037;24038;24039	chr2:178718343;178718342;178718341	chr2:179583070;179583069;179583068
N2A	7011	21256;21257;21258	chr2:178718343;178718342;178718341	chr2:179583070;179583069;179583068
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-67
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.479
• 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/A	rs794727943	-0.376	0.012	N	0.437	0.145	0.333154297509	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	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	0.1569	likely_benign	0.1469	benign	-0.749	Destabilizing	0.012	N	0.437	neutral	N	0.517820733	None	None	I
E/C	0.7952	likely_pathogenic	0.7749	pathogenic	-0.153	Destabilizing	0.001	N	0.449	neutral	None	None	None	None	I
E/D	0.1105	likely_benign	0.085	benign	-0.7	Destabilizing	None	N	0.189	neutral	N	0.49277036	None	None	I
E/F	0.6757	likely_pathogenic	0.6356	pathogenic	-0.624	Destabilizing	0.356	N	0.619	neutral	None	None	None	None	I
E/G	0.1425	likely_benign	0.1299	benign	-1.006	Destabilizing	None	N	0.36	neutral	N	0.494152707	None	None	I
E/H	0.2973	likely_benign	0.2778	benign	-0.737	Destabilizing	0.001	N	0.275	neutral	None	None	None	None	I
E/I	0.3968	ambiguous	0.3716	ambiguous	-0.082	Destabilizing	0.356	N	0.654	neutral	None	None	None	None	I
E/K	0.0995	likely_benign	0.1046	benign	-0.091	Destabilizing	0.055	N	0.446	neutral	N	0.490863418	None	None	I
E/L	0.39	ambiguous	0.3604	ambiguous	-0.082	Destabilizing	0.072	N	0.61	neutral	None	None	None	None	I
E/M	0.4497	ambiguous	0.4265	ambiguous	0.309	Stabilizing	0.864	D	0.599	neutral	None	None	None	None	I
E/N	0.1825	likely_benign	0.1533	benign	-0.407	Destabilizing	0.038	N	0.453	neutral	None	None	None	None	I
E/P	0.6959	likely_pathogenic	0.6274	pathogenic	-0.284	Destabilizing	0.356	N	0.63	neutral	None	None	None	None	I
E/Q	0.1071	likely_benign	0.1114	benign	-0.37	Destabilizing	0.055	N	0.513	neutral	N	0.493290435	None	None	I
E/R	0.1744	likely_benign	0.1798	benign	0.06	Stabilizing	0.072	N	0.561	neutral	None	None	None	None	I
E/S	0.1387	likely_benign	0.128	benign	-0.629	Destabilizing	0.001	N	0.227	neutral	None	None	None	None	I
E/T	0.1729	likely_benign	0.1625	benign	-0.422	Destabilizing	0.038	N	0.522	neutral	None	None	None	None	I
E/V	0.2342	likely_benign	0.2151	benign	-0.284	Destabilizing	0.055	N	0.636	neutral	N	0.500989562	None	None	I
E/W	0.8316	likely_pathogenic	0.7977	pathogenic	-0.441	Destabilizing	0.864	D	0.627	neutral	None	None	None	None	I
E/Y	0.5144	ambiguous	0.4627	ambiguous	-0.38	Destabilizing	0.214	N	0.624	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.