TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30775	92548;92549;92550	chr2:178549303;178549302;178549301	chr2:179414030;179414029;179414028
N2AB	29134	87625;87626;87627	chr2:178549303;178549302;178549301	chr2:179414030;179414029;179414028
N2A	28207	84844;84845;84846	chr2:178549303;178549302;178549301	chr2:179414030;179414029;179414028
N2B	21710	65353;65354;65355	chr2:178549303;178549302;178549301	chr2:179414030;179414029;179414028
Novex-1	21835	65728;65729;65730	chr2:178549303;178549302;178549301	chr2:179414030;179414029;179414028
Novex-2	21902	65929;65930;65931	chr2:178549303;178549302;178549301	chr2:179414030;179414029;179414028
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-112
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.0622
• 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
I/V	rs1410441906	-1.507	0.008	N	0.209	0.121	0.230578612272	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
I/V	rs1410441906	-1.507	0.008	N	0.209	0.121	0.230578612272	gnomAD-4.0.0	3.42082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49712E-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
I/A	0.7571	likely_pathogenic	0.7272	pathogenic	-1.936	Destabilizing	0.633	D	0.605	neutral	None	None	None	None	N
I/C	0.8929	likely_pathogenic	0.8771	pathogenic	-1.169	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N
I/D	0.9857	likely_pathogenic	0.9784	pathogenic	-1.539	Destabilizing	0.987	D	0.812	deleterious	None	None	None	None	N
I/E	0.9723	likely_pathogenic	0.9617	pathogenic	-1.314	Destabilizing	0.961	D	0.797	deleterious	None	None	None	None	N
I/F	0.497	ambiguous	0.4454	ambiguous	-0.97	Destabilizing	0.82	D	0.699	prob.neutral	N	0.498988785	None	None	N
I/G	0.9501	likely_pathogenic	0.9366	pathogenic	-2.477	Highly Destabilizing	0.961	D	0.789	deleterious	None	None	None	None	N
I/H	0.9491	likely_pathogenic	0.9314	pathogenic	-1.868	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
I/K	0.9457	likely_pathogenic	0.9269	pathogenic	-1.206	Destabilizing	0.961	D	0.797	deleterious	None	None	None	None	N
I/L	0.1842	likely_benign	0.1785	benign	-0.394	Destabilizing	0.003	N	0.243	neutral	N	0.464873603	None	None	N
I/M	0.2818	likely_benign	0.2654	benign	-0.432	Destabilizing	0.901	D	0.719	prob.delet.	N	0.492658909	None	None	N
I/N	0.8548	likely_pathogenic	0.805	pathogenic	-1.462	Destabilizing	0.983	D	0.825	deleterious	N	0.471009482	None	None	N
I/P	0.9014	likely_pathogenic	0.8815	pathogenic	-0.885	Destabilizing	0.987	D	0.815	deleterious	None	None	None	None	N
I/Q	0.9314	likely_pathogenic	0.912	pathogenic	-1.285	Destabilizing	0.987	D	0.817	deleterious	None	None	None	None	N
I/R	0.9133	likely_pathogenic	0.888	pathogenic	-1.109	Destabilizing	0.961	D	0.821	deleterious	None	None	None	None	N
I/S	0.84	likely_pathogenic	0.8059	pathogenic	-2.248	Highly Destabilizing	0.901	D	0.716	prob.delet.	N	0.514088915	None	None	N
I/T	0.8483	likely_pathogenic	0.8186	pathogenic	-1.865	Destabilizing	0.722	D	0.657	neutral	N	0.465676656	None	None	N
I/V	0.0936	likely_benign	0.0913	benign	-0.885	Destabilizing	0.008	N	0.209	neutral	N	0.419197242	None	None	N
I/W	0.9741	likely_pathogenic	0.9666	pathogenic	-1.273	Destabilizing	0.996	D	0.78	deleterious	None	None	None	None	N
I/Y	0.9039	likely_pathogenic	0.8738	pathogenic	-0.937	Destabilizing	0.961	D	0.736	prob.delet.	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.