TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4758	14497;14498;14499	chr2:178738181;178738180;178738179	chr2:179602908;179602907;179602906
N2AB	4441	13546;13547;13548	chr2:178738181;178738180;178738179	chr2:179602908;179602907;179602906
N2A	3514	10765;10766;10767	chr2:178738181;178738180;178738179	chr2:179602908;179602907;179602906
N2B	4395	13408;13409;13410	chr2:178738181;178738180;178738179	chr2:179602908;179602907;179602906
Novex-1	4520	13783;13784;13785	chr2:178738181;178738180;178738179	chr2:179602908;179602907;179602906
Novex-2	4587	13984;13985;13986	chr2:178738181;178738180;178738179	chr2:179602908;179602907;179602906
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-30
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2601
• 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	rs928709551	-0.597	0.698	N	0.511	0.321	0.327952845175	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs928709551	-0.597	0.698	N	0.511	0.321	0.327952845175	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs928709551	-0.597	0.698	N	0.511	0.321	0.327952845175	gnomAD-4.0.0	6.57203E-06	None	None	None	None	N	None	2.41324E-05	0	None	0	0	None	0	0	0	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	0.6031	likely_pathogenic	0.6703	pathogenic	-1.025	Destabilizing	0.698	D	0.55	neutral	N	0.491130694	None	None	N
E/C	0.98	likely_pathogenic	0.9832	pathogenic	-0.673	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
E/D	0.6173	likely_pathogenic	0.6883	pathogenic	-1.466	Destabilizing	0.822	D	0.482	neutral	N	0.49262601	None	None	N
E/F	0.9696	likely_pathogenic	0.9762	pathogenic	-0.609	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
E/G	0.7938	likely_pathogenic	0.8377	pathogenic	-1.43	Destabilizing	0.942	D	0.715	prob.delet.	N	0.49262601	None	None	N
E/H	0.8728	likely_pathogenic	0.8909	pathogenic	-0.97	Destabilizing	0.988	D	0.674	neutral	None	None	None	None	N
E/I	0.7925	likely_pathogenic	0.8331	pathogenic	0.097	Stabilizing	0.978	D	0.781	deleterious	None	None	None	None	N
E/K	0.7152	likely_pathogenic	0.7553	pathogenic	-1.013	Destabilizing	0.698	D	0.511	neutral	N	0.491130694	None	None	N
E/L	0.8659	likely_pathogenic	0.8989	pathogenic	0.097	Stabilizing	0.956	D	0.73	prob.delet.	None	None	None	None	N
E/M	0.8421	likely_pathogenic	0.8754	pathogenic	0.681	Stabilizing	0.994	D	0.743	deleterious	None	None	None	None	N
E/N	0.7959	likely_pathogenic	0.8515	pathogenic	-1.411	Destabilizing	0.956	D	0.638	neutral	None	None	None	None	N
E/P	0.9981	likely_pathogenic	0.9984	pathogenic	-0.257	Destabilizing	0.978	D	0.763	deleterious	None	None	None	None	N
E/Q	0.3546	ambiguous	0.4193	ambiguous	-1.23	Destabilizing	0.058	N	0.353	neutral	N	0.492248918	None	None	N
E/R	0.8001	likely_pathogenic	0.8302	pathogenic	-0.847	Destabilizing	0.915	D	0.632	neutral	None	None	None	None	N
E/S	0.6712	likely_pathogenic	0.7356	pathogenic	-1.881	Destabilizing	0.754	D	0.52	neutral	None	None	None	None	N
E/T	0.6391	likely_pathogenic	0.711	pathogenic	-1.527	Destabilizing	0.956	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.5659	likely_pathogenic	0.634	pathogenic	-0.257	Destabilizing	0.942	D	0.733	prob.delet.	N	0.490265779	None	None	N
E/W	0.9884	likely_pathogenic	0.9908	pathogenic	-0.487	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/Y	0.9454	likely_pathogenic	0.9581	pathogenic	-0.375	Destabilizing	0.978	D	0.763	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.