TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34453	103582;103583;103584	chr2:178533258;178533257;178533256	chr2:179397985;179397984;179397983
N2AB	32812	98659;98660;98661	chr2:178533258;178533257;178533256	chr2:179397985;179397984;179397983
N2A	31885	95878;95879;95880	chr2:178533258;178533257;178533256	chr2:179397985;179397984;179397983
N2B	25388	76387;76388;76389	chr2:178533258;178533257;178533256	chr2:179397985;179397984;179397983
Novex-1	25513	76762;76763;76764	chr2:178533258;178533257;178533256	chr2:179397985;179397984;179397983
Novex-2	25580	76963;76964;76965	chr2:178533258;178533257;178533256	chr2:179397985;179397984;179397983
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-162
• Domain position: 91
• Structural Position: 177
• Q(SASA): 0.2292
• 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
V/M	None	None	1.0	D	0.897	0.735	0.758961761621	gnomAD-4.0.0	1.59092E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85765E-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
V/A	0.9098	likely_pathogenic	0.8898	pathogenic	-1.563	Destabilizing	0.999	D	0.775	deleterious	D	0.627572757	None	None	N
V/C	0.9896	likely_pathogenic	0.9884	pathogenic	-1.575	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/D	0.9964	likely_pathogenic	0.9964	pathogenic	-2.962	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/E	0.9883	likely_pathogenic	0.9884	pathogenic	-2.934	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.628178169	None	None	N
V/F	0.9841	likely_pathogenic	0.983	pathogenic	-1.242	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
V/G	0.9073	likely_pathogenic	0.9075	pathogenic	-1.874	Destabilizing	1.0	D	0.885	deleterious	D	0.628178169	None	None	N
V/H	0.999	likely_pathogenic	0.9989	pathogenic	-1.405	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/I	0.3324	likely_benign	0.3002	benign	-0.776	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
V/K	0.9924	likely_pathogenic	0.9915	pathogenic	-1.407	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/L	0.9667	likely_pathogenic	0.9611	pathogenic	-0.776	Destabilizing	0.997	D	0.782	deleterious	D	0.593283827	None	None	N
V/M	0.9579	likely_pathogenic	0.9529	pathogenic	-0.792	Destabilizing	1.0	D	0.897	deleterious	D	0.595503674	None	None	N
V/N	0.9904	likely_pathogenic	0.9892	pathogenic	-1.546	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/P	0.9914	likely_pathogenic	0.9906	pathogenic	-1.01	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/Q	0.9935	likely_pathogenic	0.993	pathogenic	-1.748	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/R	0.9869	likely_pathogenic	0.9864	pathogenic	-0.903	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/S	0.9691	likely_pathogenic	0.9645	pathogenic	-1.873	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/T	0.8846	likely_pathogenic	0.8663	pathogenic	-1.75	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.557	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/Y	0.998	likely_pathogenic	0.998	pathogenic	-1.229	Destabilizing	1.0	D	0.913	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.