TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27612	83059;83060;83061	chr2:178563298;178563297;178563296	chr2:179428025;179428024;179428023
N2AB	25971	78136;78137;78138	chr2:178563298;178563297;178563296	chr2:179428025;179428024;179428023
N2A	25044	75355;75356;75357	chr2:178563298;178563297;178563296	chr2:179428025;179428024;179428023
N2B	18547	55864;55865;55866	chr2:178563298;178563297;178563296	chr2:179428025;179428024;179428023
Novex-1	18672	56239;56240;56241	chr2:178563298;178563297;178563296	chr2:179428025;179428024;179428023
Novex-2	18739	56440;56441;56442	chr2:178563298;178563297;178563296	chr2:179428025;179428024;179428023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-89
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.495
• Predicted PPI site: N

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
A/D	None	None	0.015	N	0.352	0.128	0.366277470483	gnomAD-4.0.0	2.0528E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69856E-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
A/C	0.4193	ambiguous	0.4355	ambiguous	-0.88	Destabilizing	0.996	D	0.403	neutral	None	None	None	None	N
A/D	0.2392	likely_benign	0.1997	benign	-1.054	Destabilizing	0.015	N	0.352	neutral	N	0.500567832	None	None	N
A/E	0.2074	likely_benign	0.1831	benign	-1.183	Destabilizing	0.59	D	0.331	neutral	None	None	None	None	N
A/F	0.2952	likely_benign	0.2946	benign	-1.244	Destabilizing	0.91	D	0.546	neutral	None	None	None	None	N
A/G	0.1193	likely_benign	0.1148	benign	-0.895	Destabilizing	0.521	D	0.263	neutral	N	0.464975178	None	None	N
A/H	0.4382	ambiguous	0.4059	ambiguous	-0.866	Destabilizing	0.974	D	0.523	neutral	None	None	None	None	N
A/I	0.1427	likely_benign	0.145	benign	-0.623	Destabilizing	0.082	N	0.269	neutral	None	None	None	None	N
A/K	0.3274	likely_benign	0.2898	benign	-0.98	Destabilizing	0.742	D	0.387	neutral	None	None	None	None	N
A/L	0.1434	likely_benign	0.1389	benign	-0.623	Destabilizing	0.373	N	0.323	neutral	None	None	None	None	N
A/M	0.1521	likely_benign	0.1517	benign	-0.419	Destabilizing	0.953	D	0.423	neutral	None	None	None	None	N
A/N	0.1901	likely_benign	0.1824	benign	-0.64	Destabilizing	0.02	N	0.369	neutral	None	None	None	None	N
A/P	0.2115	likely_benign	0.2025	benign	-0.636	Destabilizing	0.939	D	0.437	neutral	N	0.467764767	None	None	N
A/Q	0.2957	likely_benign	0.2704	benign	-0.974	Destabilizing	0.91	D	0.44	neutral	None	None	None	None	N
A/R	0.3637	ambiguous	0.3105	benign	-0.426	Destabilizing	0.91	D	0.443	neutral	None	None	None	None	N
A/S	0.0944	likely_benign	0.0935	benign	-0.892	Destabilizing	0.028	N	0.222	neutral	N	0.470495641	None	None	N
A/T	0.0806	likely_benign	0.0808	benign	-0.947	Destabilizing	0.028	N	0.227	neutral	N	0.489273403	None	None	N
A/V	0.0834	likely_benign	0.0842	benign	-0.636	Destabilizing	0.007	N	0.217	neutral	N	0.441788887	None	None	N
A/W	0.6824	likely_pathogenic	0.6571	pathogenic	-1.381	Destabilizing	0.996	D	0.603	neutral	None	None	None	None	N
A/Y	0.4018	ambiguous	0.3971	ambiguous	-1.048	Destabilizing	0.953	D	0.543	neutral	None	None	None	None	N

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.