TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34207	102844;102845;102846	chr2:178533996;178533995;178533994	chr2:179398723;179398722;179398721
N2AB	32566	97921;97922;97923	chr2:178533996;178533995;178533994	chr2:179398723;179398722;179398721
N2A	31639	95140;95141;95142	chr2:178533996;178533995;178533994	chr2:179398723;179398722;179398721
N2B	25142	75649;75650;75651	chr2:178533996;178533995;178533994	chr2:179398723;179398722;179398721
Novex-1	25267	76024;76025;76026	chr2:178533996;178533995;178533994	chr2:179398723;179398722;179398721
Novex-2	25334	76225;76226;76227	chr2:178533996;178533995;178533994	chr2:179398723;179398722;179398721
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-160
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0986
• 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
Y/H	None	None	1.0	D	0.785	0.87	0.601041065218	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Y/A	0.9965	likely_pathogenic	0.9958	pathogenic	-1.786	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/C	0.9502	likely_pathogenic	0.948	pathogenic	-1.029	Destabilizing	1.0	D	0.888	deleterious	D	0.596775221	None	None	N
Y/D	0.9985	likely_pathogenic	0.9983	pathogenic	-2.638	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.596775221	None	None	N
Y/E	0.9993	likely_pathogenic	0.9992	pathogenic	-2.399	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/F	0.2064	likely_benign	0.2386	benign	-0.626	Destabilizing	0.999	D	0.666	neutral	D	0.557176865	None	None	N
Y/G	0.9946	likely_pathogenic	0.9936	pathogenic	-2.209	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/H	0.9789	likely_pathogenic	0.9788	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.785	deleterious	D	0.596573416	None	None	N
Y/I	0.9404	likely_pathogenic	0.9385	pathogenic	-0.39	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9987	pathogenic	-1.501	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/L	0.8605	likely_pathogenic	0.8491	pathogenic	-0.39	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
Y/M	0.9792	likely_pathogenic	0.979	pathogenic	-0.513	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/N	0.9918	likely_pathogenic	0.9906	pathogenic	-2.412	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.596775221	None	None	N
Y/P	0.9985	likely_pathogenic	0.9981	pathogenic	-0.87	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
Y/Q	0.9989	likely_pathogenic	0.9987	pathogenic	-1.907	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/R	0.995	likely_pathogenic	0.9943	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/S	0.9895	likely_pathogenic	0.988	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.596775221	None	None	N
Y/T	0.9968	likely_pathogenic	0.9963	pathogenic	-2.192	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/V	0.9152	likely_pathogenic	0.9091	pathogenic	-0.87	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/W	0.8257	likely_pathogenic	0.8269	pathogenic	-0.117	Destabilizing	1.0	D	0.777	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.