TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7404	22435;22436;22437	chr2:178722689;178722688;178722687	chr2:179587416;179587415;179587414
N2AB	7087	21484;21485;21486	chr2:178722689;178722688;178722687	chr2:179587416;179587415;179587414
N2A	6160	18703;18704;18705	chr2:178722689;178722688;178722687	chr2:179587416;179587415;179587414
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-58
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1785
• 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/S	None	None	0.136	N	0.335	0.189	0.238705975628	gnomAD-4.0.0	6.84774E-07	None	None	None	None	I	None	0	0	None	0	2.52423E-05	None	0	0	0	0	0
A/T	None	None	0.669	N	0.42	0.249	0.337135696972	gnomAD-4.0.0	6.84774E-07	None	None	None	None	I	None	0	2.24004E-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	0.6218	likely_pathogenic	0.6373	pathogenic	-0.814	Destabilizing	0.998	D	0.484	neutral	None	None	None	None	I
A/D	0.3259	likely_benign	0.5123	ambiguous	-0.443	Destabilizing	0.028	N	0.417	neutral	N	0.507662454	None	None	I
A/E	0.3647	ambiguous	0.4595	ambiguous	-0.488	Destabilizing	0.728	D	0.48	neutral	None	None	None	None	I
A/F	0.4131	ambiguous	0.4771	ambiguous	-0.824	Destabilizing	0.949	D	0.573	neutral	None	None	None	None	I
A/G	0.2301	likely_benign	0.2853	benign	-0.939	Destabilizing	0.801	D	0.401	neutral	N	0.486950685	None	None	I
A/H	0.6099	likely_pathogenic	0.676	pathogenic	-0.951	Destabilizing	0.998	D	0.523	neutral	None	None	None	None	I
A/I	0.2453	likely_benign	0.2914	benign	-0.24	Destabilizing	0.904	D	0.5	neutral	None	None	None	None	I
A/K	0.547	ambiguous	0.6385	pathogenic	-0.866	Destabilizing	0.842	D	0.483	neutral	None	None	None	None	I
A/L	0.2946	likely_benign	0.337	benign	-0.24	Destabilizing	0.728	D	0.463	neutral	None	None	None	None	I
A/M	0.3151	likely_benign	0.3533	ambiguous	-0.301	Destabilizing	0.993	D	0.486	neutral	None	None	None	None	I
A/N	0.3644	ambiguous	0.4716	ambiguous	-0.594	Destabilizing	0.904	D	0.549	neutral	None	None	None	None	I
A/P	0.9349	likely_pathogenic	0.9662	pathogenic	-0.354	Destabilizing	0.028	N	0.321	neutral	N	0.496256302	None	None	I
A/Q	0.4773	ambiguous	0.5288	ambiguous	-0.741	Destabilizing	0.974	D	0.537	neutral	None	None	None	None	I
A/R	0.4766	ambiguous	0.543	ambiguous	-0.556	Destabilizing	0.974	D	0.533	neutral	None	None	None	None	I
A/S	0.1065	likely_benign	0.1164	benign	-1.017	Destabilizing	0.136	N	0.335	neutral	N	0.480534568	None	None	I
A/T	0.0878	likely_benign	0.0972	benign	-0.957	Destabilizing	0.669	D	0.42	neutral	N	0.48392159	None	None	I
A/V	0.1119	likely_benign	0.1287	benign	-0.354	Destabilizing	0.111	N	0.295	neutral	N	0.4698935	None	None	I
A/W	0.8777	likely_pathogenic	0.9131	pathogenic	-1.098	Destabilizing	0.081	N	0.573	neutral	None	None	None	None	I
A/Y	0.5859	likely_pathogenic	0.6677	pathogenic	-0.689	Destabilizing	0.949	D	0.567	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.