TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2241	6946;6947;6948	chr2:178774990;178774989;178774988	chr2:179639717;179639716;179639715
N2AB	2241	6946;6947;6948	chr2:178774990;178774989;178774988	chr2:179639717;179639716;179639715
N2A	2241	6946;6947;6948	chr2:178774990;178774989;178774988	chr2:179639717;179639716;179639715
N2B	2195	6808;6809;6810	chr2:178774990;178774989;178774988	chr2:179639717;179639716;179639715
Novex-1	2195	6808;6809;6810	chr2:178774990;178774989;178774988	chr2:179639717;179639716;179639715
Novex-2	2195	6808;6809;6810	chr2:178774990;178774989;178774988	chr2:179639717;179639716;179639715
Novex-3	2241	6946;6947;6948	chr2:178774990;178774989;178774988	chr2:179639717;179639716;179639715

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-11
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2263
• 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	0.005	N	0.284	0.292	0.492749560936	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	2.28697E-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
A/C	0.4822	ambiguous	0.4344	ambiguous	-0.98	Destabilizing	0.998	D	0.469	neutral	None	None	None	None	N
A/D	0.2946	likely_benign	0.293	benign	-1.065	Destabilizing	0.005	N	0.284	neutral	N	0.505214838	None	None	N
A/E	0.1703	likely_benign	0.1763	benign	-1.135	Destabilizing	0.007	N	0.204	neutral	None	None	None	None	N
A/F	0.3556	ambiguous	0.3439	ambiguous	-1.084	Destabilizing	0.991	D	0.594	neutral	None	None	None	None	N
A/G	0.1266	likely_benign	0.1265	benign	-1.078	Destabilizing	0.625	D	0.497	neutral	N	0.504746739	None	None	N
A/H	0.4839	ambiguous	0.4671	ambiguous	-1.171	Destabilizing	0.974	D	0.581	neutral	None	None	None	None	N
A/I	0.235	likely_benign	0.2184	benign	-0.472	Destabilizing	0.974	D	0.53	neutral	None	None	None	None	N
A/K	0.2772	likely_benign	0.2774	benign	-1.222	Destabilizing	0.728	D	0.483	neutral	None	None	None	None	N
A/L	0.1793	likely_benign	0.1769	benign	-0.472	Destabilizing	0.842	D	0.479	neutral	None	None	None	None	N
A/M	0.1911	likely_benign	0.1753	benign	-0.384	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	N
A/N	0.2455	likely_benign	0.2379	benign	-0.91	Destabilizing	0.842	D	0.533	neutral	None	None	None	None	N
A/P	0.62	likely_pathogenic	0.637	pathogenic	-0.564	Destabilizing	0.966	D	0.509	neutral	D	0.677136837	None	None	N
A/Q	0.2604	likely_benign	0.2566	benign	-1.124	Destabilizing	0.904	D	0.499	neutral	None	None	None	None	N
A/R	0.2495	likely_benign	0.2517	benign	-0.79	Destabilizing	0.949	D	0.515	neutral	None	None	None	None	N
A/S	0.0851	likely_benign	0.0838	benign	-1.238	Destabilizing	0.625	D	0.533	neutral	N	0.504170429	None	None	N
A/T	0.082	likely_benign	0.0784	benign	-1.219	Destabilizing	0.801	D	0.461	neutral	N	0.51334847	None	None	N
A/V	0.1371	likely_benign	0.1315	benign	-0.564	Destabilizing	0.891	D	0.465	neutral	N	0.504524326	None	None	N
A/W	0.7588	likely_pathogenic	0.7408	pathogenic	-1.343	Destabilizing	0.998	D	0.659	neutral	None	None	None	None	N
A/Y	0.4867	ambiguous	0.4683	ambiguous	-0.978	Destabilizing	0.991	D	0.594	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.