TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22600	68023;68024;68025	chr2:178579232;178579231;178579230	chr2:179443959;179443958;179443957
N2AB	20959	63100;63101;63102	chr2:178579232;178579231;178579230	chr2:179443959;179443958;179443957
N2A	20032	60319;60320;60321	chr2:178579232;178579231;178579230	chr2:179443959;179443958;179443957
N2B	13535	40828;40829;40830	chr2:178579232;178579231;178579230	chr2:179443959;179443958;179443957
Novex-1	13660	41203;41204;41205	chr2:178579232;178579231;178579230	chr2:179443959;179443958;179443957
Novex-2	13727	41404;41405;41406	chr2:178579232;178579231;178579230	chr2:179443959;179443958;179443957
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-127
• Domain position: 41
• Structural Position: 125
• Q(SASA): 0.6326
• 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
E/K	None	None	0.928	N	0.581	0.343	0.39843156188	gnomAD-4.0.0	6.84331E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99603E-07	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
E/A	0.2821	likely_benign	0.2517	benign	-0.723	Destabilizing	0.928	D	0.649	neutral	N	0.510027969	None	None	N
E/C	0.9209	likely_pathogenic	0.9138	pathogenic	0.052	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
E/D	0.1856	likely_benign	0.1717	benign	-0.382	Destabilizing	0.039	N	0.289	neutral	N	0.510027969	None	None	N
E/F	0.8273	likely_pathogenic	0.8073	pathogenic	-0.7	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
E/G	0.4004	ambiguous	0.3555	ambiguous	-0.916	Destabilizing	0.978	D	0.653	neutral	N	0.507559701	None	None	N
E/H	0.5819	likely_pathogenic	0.557	ambiguous	-0.727	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
E/I	0.4621	ambiguous	0.4296	ambiguous	-0.24	Destabilizing	0.992	D	0.727	prob.delet.	None	None	None	None	N
E/K	0.3197	likely_benign	0.2852	benign	0.355	Stabilizing	0.928	D	0.581	neutral	N	0.480262422	None	None	N
E/L	0.5705	likely_pathogenic	0.5343	ambiguous	-0.24	Destabilizing	0.992	D	0.729	prob.delet.	None	None	None	None	N
E/M	0.6117	likely_pathogenic	0.5835	pathogenic	0.147	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
E/N	0.4237	ambiguous	0.3833	ambiguous	0.005	Stabilizing	0.968	D	0.69	prob.neutral	None	None	None	None	N
E/P	0.9751	likely_pathogenic	0.9636	pathogenic	-0.383	Destabilizing	0.992	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.2035	likely_benign	0.1896	benign	0.028	Stabilizing	0.978	D	0.622	neutral	N	0.517204657	None	None	N
E/R	0.4857	ambiguous	0.4484	ambiguous	0.354	Stabilizing	0.992	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.3221	likely_benign	0.2926	benign	-0.143	Destabilizing	0.944	D	0.617	neutral	None	None	None	None	N
E/T	0.3168	likely_benign	0.2846	benign	0.03	Stabilizing	0.983	D	0.684	prob.neutral	None	None	None	None	N
E/V	0.296	likely_benign	0.268	benign	-0.383	Destabilizing	0.989	D	0.719	prob.delet.	N	0.52078368	None	None	N
E/W	0.953	likely_pathogenic	0.9479	pathogenic	-0.514	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/Y	0.7484	likely_pathogenic	0.7188	pathogenic	-0.444	Destabilizing	0.999	D	0.703	prob.neutral	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.