TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31192	93799;93800;93801	chr2:178548052;178548051;178548050	chr2:179412779;179412778;179412777
N2AB	29551	88876;88877;88878	chr2:178548052;178548051;178548050	chr2:179412779;179412778;179412777
N2A	28624	86095;86096;86097	chr2:178548052;178548051;178548050	chr2:179412779;179412778;179412777
N2B	22127	66604;66605;66606	chr2:178548052;178548051;178548050	chr2:179412779;179412778;179412777
Novex-1	22252	66979;66980;66981	chr2:178548052;178548051;178548050	chr2:179412779;179412778;179412777
Novex-2	22319	67180;67181;67182	chr2:178548052;178548051;178548050	chr2:179412779;179412778;179412777
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: Fn3-115
• Domain position: 80
• Structural Position: 114
• Q(SASA): 0.465
• 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/T	rs779450650	-0.462	0.085	N	0.448	0.16	0.137902524267	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	8.87E-06	0
A/T	rs779450650	-0.462	0.085	N	0.448	0.16	0.137902524267	gnomAD-4.0.0	1.59108E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85791E-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
A/C	0.5798	likely_pathogenic	0.526	ambiguous	-0.69	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
A/D	0.9028	likely_pathogenic	0.834	pathogenic	-0.73	Destabilizing	0.978	D	0.813	deleterious	N	0.485954321	None	None	I
A/E	0.8142	likely_pathogenic	0.7043	pathogenic	-0.903	Destabilizing	0.983	D	0.769	deleterious	None	None	None	None	I
A/F	0.5999	likely_pathogenic	0.4725	ambiguous	-0.976	Destabilizing	0.992	D	0.847	deleterious	None	None	None	None	I
A/G	0.3278	likely_benign	0.2917	benign	-0.264	Destabilizing	0.928	D	0.602	neutral	N	0.475140993	None	None	I
A/H	0.8109	likely_pathogenic	0.71	pathogenic	-0.264	Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	I
A/I	0.433	ambiguous	0.3925	ambiguous	-0.389	Destabilizing	0.983	D	0.773	deleterious	None	None	None	None	I
A/K	0.8546	likely_pathogenic	0.7753	pathogenic	-0.57	Destabilizing	0.983	D	0.775	deleterious	None	None	None	None	I
A/L	0.4792	ambiguous	0.4098	ambiguous	-0.389	Destabilizing	0.895	D	0.664	neutral	None	None	None	None	I
A/M	0.4452	ambiguous	0.37	ambiguous	-0.344	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	I
A/N	0.7021	likely_pathogenic	0.6161	pathogenic	-0.222	Destabilizing	0.983	D	0.825	deleterious	None	None	None	None	I
A/P	0.9799	likely_pathogenic	0.9695	pathogenic	-0.31	Destabilizing	0.989	D	0.771	deleterious	D	0.523772673	None	None	I
A/Q	0.7294	likely_pathogenic	0.625	pathogenic	-0.574	Destabilizing	0.992	D	0.799	deleterious	None	None	None	None	I
A/R	0.7687	likely_pathogenic	0.6587	pathogenic	-0.023	Destabilizing	0.983	D	0.783	deleterious	None	None	None	None	I
A/S	0.1617	likely_benign	0.1555	benign	-0.367	Destabilizing	0.865	D	0.516	neutral	N	0.505187004	None	None	I
A/T	0.205	likely_benign	0.1811	benign	-0.473	Destabilizing	0.085	N	0.448	neutral	N	0.486714789	None	None	I
A/V	0.2004	likely_benign	0.1766	benign	-0.31	Destabilizing	0.865	D	0.63	neutral	N	0.492929783	None	None	I
A/W	0.9504	likely_pathogenic	0.9046	pathogenic	-1.077	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	I
A/Y	0.8124	likely_pathogenic	0.7013	pathogenic	-0.736	Destabilizing	0.999	D	0.845	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.