TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17358	52297;52298;52299	chr2:178609238;178609237;178609236	chr2:179473965;179473964;179473963
N2AB	15717	47374;47375;47376	chr2:178609238;178609237;178609236	chr2:179473965;179473964;179473963
N2A	14790	44593;44594;44595	chr2:178609238;178609237;178609236	chr2:179473965;179473964;179473963
N2B	8293	25102;25103;25104	chr2:178609238;178609237;178609236	chr2:179473965;179473964;179473963
Novex-1	8418	25477;25478;25479	chr2:178609238;178609237;178609236	chr2:179473965;179473964;179473963
Novex-2	8485	25678;25679;25680	chr2:178609238;178609237;178609236	chr2:179473965;179473964;179473963
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-112
• Domain position: 108
• Structural Position: 166
• Q(SASA): 0.3037
• 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
A/V	None	None	0.235	N	0.347	0.289	0.480123561213	gnomAD-4.0.0	7.2825E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.32151E-07	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	0.5419	ambiguous	0.5573	ambiguous	-0.866	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
A/D	0.5719	likely_pathogenic	0.528	ambiguous	-0.946	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	I
A/E	0.5109	ambiguous	0.4926	ambiguous	-1.021	Destabilizing	0.997	D	0.825	deleterious	N	0.485074127	None	None	I
A/F	0.5914	likely_pathogenic	0.5793	pathogenic	-0.79	Destabilizing	0.998	D	0.873	deleterious	None	None	None	None	I
A/G	0.2744	likely_benign	0.281	benign	-0.733	Destabilizing	0.989	D	0.578	neutral	N	0.500940337	None	None	I
A/H	0.7167	likely_pathogenic	0.7112	pathogenic	-0.694	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
A/I	0.4393	ambiguous	0.4332	ambiguous	-0.293	Destabilizing	0.966	D	0.736	prob.delet.	None	None	None	None	I
A/K	0.7079	likely_pathogenic	0.6886	pathogenic	-1.119	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
A/L	0.3519	ambiguous	0.3657	ambiguous	-0.293	Destabilizing	0.966	D	0.598	neutral	None	None	None	None	I
A/M	0.4094	ambiguous	0.4218	ambiguous	-0.437	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	I
A/N	0.5701	likely_pathogenic	0.5715	pathogenic	-0.884	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	I
A/P	0.9768	likely_pathogenic	0.97	pathogenic	-0.346	Destabilizing	0.999	D	0.845	deleterious	N	0.497572975	None	None	I
A/Q	0.5111	ambiguous	0.5167	ambiguous	-1.083	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	I
A/R	0.6275	likely_pathogenic	0.6108	pathogenic	-0.636	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	I
A/S	0.1253	likely_benign	0.1296	benign	-1.115	Destabilizing	0.989	D	0.591	neutral	D	0.534945056	None	None	I
A/T	0.135	likely_benign	0.1341	benign	-1.104	Destabilizing	0.977	D	0.681	prob.neutral	N	0.496559017	None	None	I
A/V	0.2286	likely_benign	0.2193	benign	-0.346	Destabilizing	0.235	N	0.347	neutral	N	0.482414327	None	None	I
A/W	0.9191	likely_pathogenic	0.9185	pathogenic	-1.05	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
A/Y	0.735	likely_pathogenic	0.7328	pathogenic	-0.678	Destabilizing	0.999	D	0.869	deleterious	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.