TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16641	50146;50147;50148	chr2:178612800;178612799;178612798	chr2:179477527;179477526;179477525
N2AB	15000	45223;45224;45225	chr2:178612800;178612799;178612798	chr2:179477527;179477526;179477525
N2A	14073	42442;42443;42444	chr2:178612800;178612799;178612798	chr2:179477527;179477526;179477525
N2B	7576	22951;22952;22953	chr2:178612800;178612799;178612798	chr2:179477527;179477526;179477525
Novex-1	7701	23326;23327;23328	chr2:178612800;178612799;178612798	chr2:179477527;179477526;179477525
Novex-2	7768	23527;23528;23529	chr2:178612800;178612799;178612798	chr2:179477527;179477526;179477525
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-8
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.8448
• 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
D/G	None	None	0.996	N	0.811	0.423	0.439339381091	gnomAD-4.0.0	1.2004E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31256E-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
D/A	0.2834	likely_benign	0.3642	ambiguous	-0.07	Destabilizing	0.997	D	0.717	prob.delet.	N	0.504864722	None	None	N
D/C	0.8568	likely_pathogenic	0.9077	pathogenic	0.202	Stabilizing	1.0	D	0.73	deleterious	None	None	None	None	N
D/E	0.1897	likely_benign	0.197	benign	-0.18	Destabilizing	0.603	D	0.249	neutral	N	0.423965343	None	None	N
D/F	0.7657	likely_pathogenic	0.8447	pathogenic	-0.183	Destabilizing	1.0	D	0.698	prob.delet.	None	None	None	None	N
D/G	0.3795	ambiguous	0.494	ambiguous	-0.212	Destabilizing	0.996	D	0.811	deleterious	N	0.507947474	None	None	N
D/H	0.5489	ambiguous	0.69	pathogenic	0.067	Stabilizing	1.0	D	0.688	prob.delet.	D	0.630545705	None	None	N
D/I	0.5095	ambiguous	0.6136	pathogenic	0.24	Stabilizing	1.0	D	0.725	deleterious	None	None	None	None	N
D/K	0.5582	ambiguous	0.7115	pathogenic	0.555	Stabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
D/L	0.4849	ambiguous	0.5919	pathogenic	0.24	Stabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	N
D/M	0.7589	likely_pathogenic	0.8162	pathogenic	0.309	Stabilizing	1.0	D	0.732	deleterious	None	None	None	None	N
D/N	0.1737	likely_benign	0.2251	benign	0.349	Stabilizing	0.999	D	0.783	deleterious	N	0.507026414	None	None	N
D/P	0.6144	likely_pathogenic	0.6889	pathogenic	0.157	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
D/Q	0.5035	ambiguous	0.6155	pathogenic	0.36	Stabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
D/R	0.6595	likely_pathogenic	0.7983	pathogenic	0.62	Stabilizing	0.998	D	0.694	prob.delet.	None	None	None	None	N
D/S	0.1928	likely_benign	0.2557	benign	0.263	Stabilizing	0.993	D	0.756	deleterious	None	None	None	None	N
D/T	0.3909	ambiguous	0.4677	ambiguous	0.375	Stabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
D/V	0.3346	likely_benign	0.435	ambiguous	0.157	Stabilizing	0.999	D	0.725	deleterious	N	0.508387648	None	None	N
D/W	0.9613	likely_pathogenic	0.9781	pathogenic	-0.129	Destabilizing	1.0	D	0.669	prob.neutral	None	None	None	None	N
D/Y	0.4653	ambiguous	0.6014	pathogenic	0.042	Stabilizing	1.0	D	0.699	prob.delet.	D	0.670339108	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.