TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30945	93058;93059;93060	chr2:178548793;178548792;178548791	chr2:179413520;179413519;179413518
N2AB	29304	88135;88136;88137	chr2:178548793;178548792;178548791	chr2:179413520;179413519;179413518
N2A	28377	85354;85355;85356	chr2:178548793;178548792;178548791	chr2:179413520;179413519;179413518
N2B	21880	65863;65864;65865	chr2:178548793;178548792;178548791	chr2:179413520;179413519;179413518
Novex-1	22005	66238;66239;66240	chr2:178548793;178548792;178548791	chr2:179413520;179413519;179413518
Novex-2	22072	66439;66440;66441	chr2:178548793;178548792;178548791	chr2:179413520;179413519;179413518
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-150
• Domain position: 19
• Structural Position: 30
• Q(SASA): 0.1781
• 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
L/F	None	None	1.0	N	0.771	0.417	0.732157991247	gnomAD-4.0.0	4.78217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71667E-06	1.43275E-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
L/A	0.9586	likely_pathogenic	0.9565	pathogenic	-1.916	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
L/C	0.9214	likely_pathogenic	0.9184	pathogenic	-1.375	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.999	pathogenic	-2.798	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/E	0.9962	likely_pathogenic	0.996	pathogenic	-2.536	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/F	0.57	likely_pathogenic	0.5925	pathogenic	-1.331	Destabilizing	1.0	D	0.771	deleterious	N	0.486209747	None	None	N
L/G	0.9906	likely_pathogenic	0.9896	pathogenic	-2.386	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9802	likely_pathogenic	0.981	pathogenic	-2.243	Highly Destabilizing	1.0	D	0.82	deleterious	D	0.602682931	None	None	N
L/I	0.1873	likely_benign	0.1996	benign	-0.511	Destabilizing	0.999	D	0.587	neutral	N	0.504156616	None	None	N
L/K	0.9905	likely_pathogenic	0.9903	pathogenic	-1.516	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/M	0.2647	likely_benign	0.2851	benign	-0.734	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
L/N	0.9928	likely_pathogenic	0.9923	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/P	0.9946	likely_pathogenic	0.9937	pathogenic	-0.971	Destabilizing	1.0	D	0.843	deleterious	D	0.602682931	None	None	N
L/Q	0.98	likely_pathogenic	0.979	pathogenic	-1.828	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/R	0.9834	likely_pathogenic	0.9821	pathogenic	-1.736	Destabilizing	1.0	D	0.831	deleterious	D	0.602682931	None	None	N
L/S	0.9923	likely_pathogenic	0.9919	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/T	0.9765	likely_pathogenic	0.9736	pathogenic	-2.14	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/V	0.3255	likely_benign	0.3343	benign	-0.971	Destabilizing	0.999	D	0.601	neutral	D	0.544097076	None	None	N
L/W	0.9519	likely_pathogenic	0.9547	pathogenic	-1.673	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/Y	0.9426	likely_pathogenic	0.946	pathogenic	-1.392	Destabilizing	1.0	D	0.783	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.