TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5233	15922;15923;15924	chr2:178733692;178733691;178733690	chr2:179598419;179598418;179598417
N2AB	4916	14971;14972;14973	chr2:178733692;178733691;178733690	chr2:179598419;179598418;179598417
N2A	3989	12190;12191;12192	chr2:178733692;178733691;178733690	chr2:179598419;179598418;179598417
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-35
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.4938
• 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
S/G	None	None	0.007	N	0.198	0.074	0.233785782151	gnomAD-4.0.0	1.59119E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85817E-06	0	0
S/R	None	None	0.884	N	0.33	0.126	0.343560092441	gnomAD-4.0.0	1.59119E-06	None	None	None	None	I	None	5.65419E-05	0	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
S/A	0.079	likely_benign	0.0837	benign	-0.217	Destabilizing	0.373	N	0.409	neutral	None	None	None	None	I
S/C	0.118	likely_benign	0.1357	benign	-0.458	Destabilizing	0.994	D	0.377	neutral	D	0.59733168	None	None	I
S/D	0.145	likely_benign	0.1713	benign	0.458	Stabilizing	0.59	D	0.296	neutral	None	None	None	None	I
S/E	0.24	likely_benign	0.2664	benign	0.384	Stabilizing	0.742	D	0.286	neutral	None	None	None	None	I
S/F	0.1718	likely_benign	0.2086	benign	-0.913	Destabilizing	0.953	D	0.402	neutral	None	None	None	None	I
S/G	0.0691	likely_benign	0.0719	benign	-0.297	Destabilizing	0.007	N	0.198	neutral	N	0.450519715	None	None	I
S/H	0.1735	likely_benign	0.2031	benign	-0.505	Destabilizing	0.02	N	0.297	neutral	None	None	None	None	I
S/I	0.1038	likely_benign	0.1193	benign	-0.137	Destabilizing	0.939	D	0.411	neutral	D	0.574248589	None	None	I
S/K	0.3118	likely_benign	0.3533	ambiguous	-0.197	Destabilizing	0.742	D	0.309	neutral	None	None	None	None	I
S/L	0.1009	likely_benign	0.1132	benign	-0.137	Destabilizing	0.742	D	0.369	neutral	None	None	None	None	I
S/M	0.1824	likely_benign	0.203	benign	-0.313	Destabilizing	0.996	D	0.343	neutral	None	None	None	None	I
S/N	0.0743	likely_benign	0.0744	benign	-0.136	Destabilizing	0.003	N	0.183	neutral	N	0.455020772	None	None	I
S/P	0.1188	likely_benign	0.1368	benign	-0.138	Destabilizing	0.984	D	0.337	neutral	None	None	None	None	I
S/Q	0.258	likely_benign	0.2864	benign	-0.258	Destabilizing	0.91	D	0.342	neutral	None	None	None	None	I
S/R	0.246	likely_benign	0.2849	benign	0.009	Stabilizing	0.884	D	0.33	neutral	N	0.447548311	None	None	I
S/T	0.0723	likely_benign	0.0801	benign	-0.231	Destabilizing	0.684	D	0.355	neutral	N	0.458135937	None	None	I
S/V	0.1304	likely_benign	0.1533	benign	-0.138	Destabilizing	0.953	D	0.381	neutral	None	None	None	None	I
S/W	0.2679	likely_benign	0.3275	benign	-1.007	Destabilizing	0.996	D	0.554	neutral	None	None	None	None	I
S/Y	0.1436	likely_benign	0.1703	benign	-0.659	Destabilizing	0.835	D	0.409	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.