TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15312	46159;46160;46161	chr2:178620587;178620586;178620585	chr2:179485314;179485313;179485312
N2AB	13671	41236;41237;41238	chr2:178620587;178620586;178620585	chr2:179485314;179485313;179485312
N2A	12744	38455;38456;38457	chr2:178620587;178620586;178620585	chr2:179485314;179485313;179485312
N2B	6247	18964;18965;18966	chr2:178620587;178620586;178620585	chr2:179485314;179485313;179485312
Novex-1	6372	19339;19340;19341	chr2:178620587;178620586;178620585	chr2:179485314;179485313;179485312
Novex-2	6439	19540;19541;19542	chr2:178620587;178620586;178620585	chr2:179485314;179485313;179485312
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-105
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.451
• 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	0.978	N	0.508	0.447	0.416581338634	gnomAD-4.0.0	1.59785E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86878E-06	0	0
E/Q	rs748340315	0.024	0.989	N	0.484	0.294	0.409124616982	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.3E-05	None	0	0	0
E/Q	rs748340315	0.024	0.989	N	0.484	0.294	0.409124616982	gnomAD-4.0.0	3.19569E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.87737E-05	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	0.4095	ambiguous	0.3844	ambiguous	-0.308	Destabilizing	0.989	D	0.486	neutral	N	0.514475193	None	None	N
E/C	0.9611	likely_pathogenic	0.9666	pathogenic	-0.145	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/D	0.3756	ambiguous	0.4184	ambiguous	-0.352	Destabilizing	0.054	N	0.186	neutral	N	0.508310303	None	None	N
E/F	0.9442	likely_pathogenic	0.9421	pathogenic	0.05	Stabilizing	0.999	D	0.638	neutral	None	None	None	None	N
E/G	0.5271	ambiguous	0.4992	ambiguous	-0.535	Destabilizing	0.978	D	0.487	neutral	D	0.587997354	None	None	N
E/H	0.8184	likely_pathogenic	0.7932	pathogenic	0.364	Stabilizing	0.999	D	0.463	neutral	None	None	None	None	N
E/I	0.7016	likely_pathogenic	0.7094	pathogenic	0.266	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	N
E/K	0.3908	ambiguous	0.3171	benign	0.454	Stabilizing	0.978	D	0.508	neutral	N	0.498845922	None	None	N
E/L	0.7722	likely_pathogenic	0.7605	pathogenic	0.266	Stabilizing	0.998	D	0.605	neutral	None	None	None	None	N
E/M	0.7795	likely_pathogenic	0.772	pathogenic	0.225	Stabilizing	1.0	D	0.565	neutral	None	None	None	None	N
E/N	0.6469	likely_pathogenic	0.6462	pathogenic	-0.125	Destabilizing	0.983	D	0.474	neutral	None	None	None	None	N
E/P	0.8861	likely_pathogenic	0.8938	pathogenic	0.096	Stabilizing	0.999	D	0.521	neutral	None	None	None	None	N
E/Q	0.29	likely_benign	0.2639	benign	-0.044	Destabilizing	0.989	D	0.484	neutral	N	0.510570465	None	None	N
E/R	0.5606	ambiguous	0.4842	ambiguous	0.725	Stabilizing	0.998	D	0.477	neutral	None	None	None	None	N
E/S	0.4837	ambiguous	0.4738	ambiguous	-0.245	Destabilizing	0.983	D	0.477	neutral	None	None	None	None	N
E/T	0.477	ambiguous	0.4568	ambiguous	-0.043	Destabilizing	0.992	D	0.485	neutral	None	None	None	None	N
E/V	0.4694	ambiguous	0.4702	ambiguous	0.096	Stabilizing	0.999	D	0.508	neutral	N	0.501957243	None	None	N
E/W	0.9809	likely_pathogenic	0.9795	pathogenic	0.266	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/Y	0.8987	likely_pathogenic	0.8875	pathogenic	0.32	Stabilizing	0.999	D	0.595	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.