TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34161	102706;102707;102708	chr2:178534134;178534133;178534132	chr2:179398861;179398860;179398859
N2AB	32520	97783;97784;97785	chr2:178534134;178534133;178534132	chr2:179398861;179398860;179398859
N2A	31593	95002;95003;95004	chr2:178534134;178534133;178534132	chr2:179398861;179398860;179398859
N2B	25096	75511;75512;75513	chr2:178534134;178534133;178534132	chr2:179398861;179398860;179398859
Novex-1	25221	75886;75887;75888	chr2:178534134;178534133;178534132	chr2:179398861;179398860;179398859
Novex-2	25288	76087;76088;76089	chr2:178534134;178534133;178534132	chr2:179398861;179398860;179398859
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-160
• Domain position: 25
• Structural Position: 39
• Q(SASA): 0.4105
• 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/Y	rs1278747931	-0.507	1.0	D	0.65	0.491	0.432266382184	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
N/Y	rs1278747931	-0.507	1.0	D	0.65	0.491	0.432266382184	gnomAD-4.0.0	3.18194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71543E-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
N/A	0.7686	likely_pathogenic	0.7423	pathogenic	-0.324	Destabilizing	0.997	D	0.56	neutral	None	None	None	None	N
N/C	0.8511	likely_pathogenic	0.8482	pathogenic	0.231	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
N/D	0.4437	ambiguous	0.3909	ambiguous	0.188	Stabilizing	0.998	D	0.616	neutral	N	0.497040029	None	None	N
N/E	0.8113	likely_pathogenic	0.7617	pathogenic	0.203	Stabilizing	0.998	D	0.633	neutral	None	None	None	None	N
N/F	0.9233	likely_pathogenic	0.9068	pathogenic	-0.477	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
N/G	0.6775	likely_pathogenic	0.6339	pathogenic	-0.557	Destabilizing	0.998	D	0.533	neutral	None	None	None	None	N
N/H	0.35	ambiguous	0.2942	benign	-0.492	Destabilizing	1.0	D	0.695	prob.neutral	N	0.508681175	None	None	N
N/I	0.8512	likely_pathogenic	0.8381	pathogenic	0.216	Stabilizing	0.999	D	0.67	neutral	N	0.508681175	None	None	N
N/K	0.7743	likely_pathogenic	0.6662	pathogenic	-0.034	Destabilizing	0.998	D	0.635	neutral	N	0.508334458	None	None	N
N/L	0.8097	likely_pathogenic	0.7891	pathogenic	0.216	Stabilizing	0.999	D	0.621	neutral	None	None	None	None	N
N/M	0.8551	likely_pathogenic	0.8396	pathogenic	0.31	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	N
N/P	0.968	likely_pathogenic	0.9679	pathogenic	0.065	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
N/Q	0.7642	likely_pathogenic	0.6963	pathogenic	-0.381	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
N/R	0.8035	likely_pathogenic	0.7082	pathogenic	-0.066	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
N/S	0.3323	likely_benign	0.3234	benign	-0.309	Destabilizing	0.992	D	0.517	neutral	N	0.453846612	None	None	N
N/T	0.5907	likely_pathogenic	0.5712	pathogenic	-0.135	Destabilizing	0.767	D	0.275	neutral	D	0.526920219	None	None	N
N/V	0.8594	likely_pathogenic	0.8505	pathogenic	0.065	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
N/W	0.9719	likely_pathogenic	0.9664	pathogenic	-0.448	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
N/Y	0.4559	ambiguous	0.3964	ambiguous	-0.188	Destabilizing	1.0	D	0.65	neutral	D	0.527440294	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.