TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20558	61897;61898;61899	chr2:178590053;178590052;178590051	chr2:179454780;179454779;179454778
N2AB	18917	56974;56975;56976	chr2:178590053;178590052;178590051	chr2:179454780;179454779;179454778
N2A	17990	54193;54194;54195	chr2:178590053;178590052;178590051	chr2:179454780;179454779;179454778
N2B	11493	34702;34703;34704	chr2:178590053;178590052;178590051	chr2:179454780;179454779;179454778
Novex-1	11618	35077;35078;35079	chr2:178590053;178590052;178590051	chr2:179454780;179454779;179454778
Novex-2	11685	35278;35279;35280	chr2:178590053;178590052;178590051	chr2:179454780;179454779;179454778
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-121
• Domain position: 80
• Structural Position: 166
• Q(SASA): 0.2491
• 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/V	None	None	1.0	N	0.681	0.412	0.461759001683	gnomAD-4.0.0	1.59271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43361E-05	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	0.432	ambiguous	0.4449	ambiguous	-0.724	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
A/D	0.7394	likely_pathogenic	0.8045	pathogenic	-0.754	Destabilizing	1.0	D	0.811	deleterious	N	0.502544636	None	None	N
A/E	0.6615	likely_pathogenic	0.7427	pathogenic	-0.917	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/F	0.4812	ambiguous	0.5389	ambiguous	-0.955	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
A/G	0.1979	likely_benign	0.2243	benign	-0.329	Destabilizing	1.0	D	0.576	neutral	N	0.52134877	None	None	N
A/H	0.6716	likely_pathogenic	0.7208	pathogenic	-0.369	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
A/I	0.4114	ambiguous	0.4638	ambiguous	-0.377	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
A/K	0.6475	likely_pathogenic	0.7179	pathogenic	-0.701	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
A/L	0.362	ambiguous	0.4114	ambiguous	-0.377	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
A/M	0.3778	ambiguous	0.4145	ambiguous	-0.384	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/N	0.5933	likely_pathogenic	0.6555	pathogenic	-0.346	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
A/P	0.9787	likely_pathogenic	0.9888	pathogenic	-0.315	Destabilizing	1.0	D	0.803	deleterious	N	0.51485431	None	None	N
A/Q	0.5043	ambiguous	0.557	ambiguous	-0.671	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
A/R	0.5466	ambiguous	0.6251	pathogenic	-0.169	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/S	0.1205	likely_benign	0.1327	benign	-0.491	Destabilizing	1.0	D	0.591	neutral	D	0.526325573	None	None	N
A/T	0.1297	likely_benign	0.1419	benign	-0.584	Destabilizing	1.0	D	0.73	prob.delet.	N	0.519746317	None	None	N
A/V	0.1985	likely_benign	0.2255	benign	-0.315	Destabilizing	1.0	D	0.681	prob.neutral	N	0.497098744	None	None	N
A/W	0.9087	likely_pathogenic	0.9295	pathogenic	-1.086	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
A/Y	0.6921	likely_pathogenic	0.741	pathogenic	-0.744	Destabilizing	1.0	D	0.805	deleterious	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.