TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7685	23278;23279;23280	chr2:178720966;178720965;178720964	chr2:179585693;179585692;179585691
N2AB	7368	22327;22328;22329	chr2:178720966;178720965;178720964	chr2:179585693;179585692;179585691
N2A	6441	19546;19547;19548	chr2:178720966;178720965;178720964	chr2:179585693;179585692;179585691
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-61
• Domain position: 78
• Structural Position: 161
• Q(SASA): 0.1473
• 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
N/D	None	None	0.996	D	0.601	0.596	0.492267288202	gnomAD-4.0.0	1.37507E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80841E-06	0	0
N/S	None	None	0.996	N	0.567	0.502	0.366848117066	gnomAD-4.0.0	1.60947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43972E-05	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
N/A	0.9642	likely_pathogenic	0.9683	pathogenic	-0.637	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
N/C	0.8939	likely_pathogenic	0.9069	pathogenic	0.062	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
N/D	0.9398	likely_pathogenic	0.9453	pathogenic	-1.157	Destabilizing	0.996	D	0.601	neutral	D	0.557690232	None	None	N
N/E	0.9947	likely_pathogenic	0.9949	pathogenic	-1.061	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
N/F	0.997	likely_pathogenic	0.997	pathogenic	-0.419	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
N/G	0.9286	likely_pathogenic	0.9379	pathogenic	-0.974	Destabilizing	1.0	D	0.542	neutral	None	None	None	None	N
N/H	0.9012	likely_pathogenic	0.9109	pathogenic	-0.884	Destabilizing	1.0	D	0.728	prob.delet.	D	0.547601374	None	None	N
N/I	0.973	likely_pathogenic	0.977	pathogenic	0.219	Stabilizing	1.0	D	0.717	prob.delet.	D	0.559211169	None	None	N
N/K	0.9941	likely_pathogenic	0.9951	pathogenic	-0.338	Destabilizing	1.0	D	0.713	prob.delet.	D	0.5584507	None	None	N
N/L	0.9406	likely_pathogenic	0.9417	pathogenic	0.219	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
N/M	0.9802	likely_pathogenic	0.9808	pathogenic	0.715	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
N/P	0.9814	likely_pathogenic	0.9834	pathogenic	-0.036	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
N/Q	0.9909	likely_pathogenic	0.9919	pathogenic	-0.977	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
N/R	0.9885	likely_pathogenic	0.9907	pathogenic	-0.378	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
N/S	0.3438	ambiguous	0.376	ambiguous	-0.865	Destabilizing	0.996	D	0.567	neutral	N	0.48491759	None	None	N
N/T	0.7512	likely_pathogenic	0.7812	pathogenic	-0.602	Destabilizing	0.998	D	0.681	prob.neutral	D	0.539839466	None	None	N
N/V	0.9657	likely_pathogenic	0.9692	pathogenic	-0.036	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
N/W	0.9987	likely_pathogenic	0.9988	pathogenic	-0.274	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
N/Y	0.9721	likely_pathogenic	0.9751	pathogenic	-0.013	Destabilizing	1.0	D	0.735	prob.delet.	D	0.547601374	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.