TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6784	20575;20576;20577	chr2:178725972;178725971;178725970	chr2:179590699;179590698;179590697
N2AB	6467	19624;19625;19626	chr2:178725972;178725971;178725970	chr2:179590699;179590698;179590697
N2A	5540	16843;16844;16845	chr2:178725972;178725971;178725970	chr2:179590699;179590698;179590697
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-52
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0944
• 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
L/F	None	None	0.969	N	0.783	0.309	0.371903410333	gnomAD-4.0.0	1.37097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80139E-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
L/A	0.7966	likely_pathogenic	0.8444	pathogenic	-2.324	Highly Destabilizing	0.924	D	0.727	prob.delet.	None	None	None	None	N
L/C	0.8402	likely_pathogenic	0.8925	pathogenic	-1.797	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/D	0.9951	likely_pathogenic	0.9968	pathogenic	-2.189	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/E	0.9755	likely_pathogenic	0.9822	pathogenic	-1.944	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/F	0.3242	likely_benign	0.3524	ambiguous	-1.379	Destabilizing	0.969	D	0.783	deleterious	N	0.517647374	None	None	N
L/G	0.9622	likely_pathogenic	0.9752	pathogenic	-2.88	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/H	0.925	likely_pathogenic	0.9449	pathogenic	-2.345	Highly Destabilizing	0.999	D	0.827	deleterious	N	0.494962401	None	None	N
L/I	0.0735	likely_benign	0.0709	benign	-0.712	Destabilizing	0.001	N	0.236	neutral	N	0.438084939	None	None	N
L/K	0.9584	likely_pathogenic	0.9676	pathogenic	-1.454	Destabilizing	0.995	D	0.816	deleterious	None	None	None	None	N
L/M	0.2239	likely_benign	0.22	benign	-0.892	Destabilizing	0.925	D	0.755	deleterious	None	None	None	None	N
L/N	0.9643	likely_pathogenic	0.9734	pathogenic	-1.81	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/P	0.9654	likely_pathogenic	0.9783	pathogenic	-1.231	Destabilizing	1.0	D	0.846	deleterious	N	0.497330817	None	None	N
L/Q	0.9182	likely_pathogenic	0.9367	pathogenic	-1.622	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/R	0.9224	likely_pathogenic	0.9402	pathogenic	-1.363	Destabilizing	1.0	D	0.807	deleterious	N	0.501710351	None	None	N
L/S	0.943	likely_pathogenic	0.9614	pathogenic	-2.603	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/T	0.8083	likely_pathogenic	0.8581	pathogenic	-2.2	Highly Destabilizing	0.898	D	0.775	deleterious	None	None	None	None	N
L/V	0.108	likely_benign	0.1121	benign	-1.231	Destabilizing	0.005	N	0.245	neutral	N	0.380241783	None	None	N
L/W	0.8199	likely_pathogenic	0.8616	pathogenic	-1.673	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/Y	0.7996	likely_pathogenic	0.8336	pathogenic	-1.387	Destabilizing	0.907	D	0.791	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.