TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14943	45052;45053;45054	chr2:178622756;178622755;178622754	chr2:179487483;179487482;179487481
N2AB	13302	40129;40130;40131	chr2:178622756;178622755;178622754	chr2:179487483;179487482;179487481
N2A	12375	37348;37349;37350	chr2:178622756;178622755;178622754	chr2:179487483;179487482;179487481
N2B	5878	17857;17858;17859	chr2:178622756;178622755;178622754	chr2:179487483;179487482;179487481
Novex-1	6003	18232;18233;18234	chr2:178622756;178622755;178622754	chr2:179487483;179487482;179487481
Novex-2	6070	18433;18434;18435	chr2:178622756;178622755;178622754	chr2:179487483;179487482;179487481
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-101
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6011
• 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/G	None	None	0.978	D	0.639	0.55	0.515317749148	gnomAD-4.0.0	1.38022E-06	None	None	None	None	N	None	3.01386E-05	0	None	0	0	None	0	0	9.04624E-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	0.2519	likely_benign	0.2355	benign	-0.307	Destabilizing	0.928	D	0.602	neutral	N	0.500899893	None	None	N
E/C	0.926	likely_pathogenic	0.9112	pathogenic	-0.211	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
E/D	0.2125	likely_benign	0.1812	benign	-0.359	Destabilizing	0.039	N	0.187	neutral	N	0.512600149	None	None	N
E/F	0.8671	likely_pathogenic	0.8442	pathogenic	0.064	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
E/G	0.3704	ambiguous	0.335	benign	-0.526	Destabilizing	0.978	D	0.639	neutral	D	0.641351339	None	None	N
E/H	0.6202	likely_pathogenic	0.5956	pathogenic	0.496	Stabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
E/I	0.5183	ambiguous	0.5058	ambiguous	0.245	Stabilizing	0.992	D	0.721	prob.delet.	None	None	None	None	N
E/K	0.2784	likely_benign	0.2511	benign	0.424	Stabilizing	0.928	D	0.539	neutral	N	0.507903935	None	None	N
E/L	0.639	likely_pathogenic	0.623	pathogenic	0.245	Stabilizing	0.992	D	0.699	prob.neutral	None	None	None	None	N
E/M	0.6346	likely_pathogenic	0.6172	pathogenic	0.163	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
E/N	0.4216	ambiguous	0.3745	ambiguous	-0.172	Destabilizing	0.968	D	0.696	prob.neutral	None	None	None	None	N
E/P	0.8631	likely_pathogenic	0.8542	pathogenic	0.081	Stabilizing	0.992	D	0.716	prob.delet.	None	None	None	None	N
E/Q	0.1992	likely_benign	0.1954	benign	-0.09	Destabilizing	0.978	D	0.638	neutral	D	0.548002332	None	None	N
E/R	0.399	ambiguous	0.3811	ambiguous	0.757	Stabilizing	0.992	D	0.703	prob.neutral	None	None	None	None	N
E/S	0.3031	likely_benign	0.2783	benign	-0.295	Destabilizing	0.944	D	0.576	neutral	None	None	None	None	N
E/T	0.2921	likely_benign	0.2677	benign	-0.097	Destabilizing	0.983	D	0.705	prob.neutral	None	None	None	None	N
E/V	0.2904	likely_benign	0.2861	benign	0.081	Stabilizing	0.989	D	0.679	prob.neutral	D	0.580646384	None	None	N
E/W	0.9607	likely_pathogenic	0.9511	pathogenic	0.284	Stabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
E/Y	0.7694	likely_pathogenic	0.7436	pathogenic	0.335	Stabilizing	0.999	D	0.692	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.