TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33036	99331;99332;99333	chr2:178538723;178538722;178538721	chr2:179403450;179403449;179403448
N2AB	31395	94408;94409;94410	chr2:178538723;178538722;178538721	chr2:179403450;179403449;179403448
N2A	30468	91627;91628;91629	chr2:178538723;178538722;178538721	chr2:179403450;179403449;179403448
N2B	23971	72136;72137;72138	chr2:178538723;178538722;178538721	chr2:179403450;179403449;179403448
Novex-1	24096	72511;72512;72513	chr2:178538723;178538722;178538721	chr2:179403450;179403449;179403448
Novex-2	24163	72712;72713;72714	chr2:178538723;178538722;178538721	chr2:179403450;179403449;179403448
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: Fn3-129
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0934
• 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	0.999	N	0.708	0.435	0.461323234107	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	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	0.8443	likely_pathogenic	0.8778	pathogenic	-0.716	Destabilizing	0.999	D	0.701	prob.neutral	D	0.525316382	None	None	N
E/C	0.99	likely_pathogenic	0.9914	pathogenic	0.007	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/D	0.8813	likely_pathogenic	0.8866	pathogenic	-1.379	Destabilizing	0.999	D	0.665	neutral	N	0.495298085	None	None	N
E/F	0.9926	likely_pathogenic	0.9941	pathogenic	-0.372	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/G	0.9244	likely_pathogenic	0.9346	pathogenic	-1.134	Destabilizing	1.0	D	0.746	deleterious	D	0.527090809	None	None	N
E/H	0.9863	likely_pathogenic	0.9882	pathogenic	-0.293	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/I	0.9606	likely_pathogenic	0.9743	pathogenic	0.471	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/K	0.968	likely_pathogenic	0.9766	pathogenic	-0.634	Destabilizing	0.999	D	0.708	prob.delet.	N	0.502652997	None	None	N
E/L	0.9747	likely_pathogenic	0.9839	pathogenic	0.471	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/M	0.9616	likely_pathogenic	0.9724	pathogenic	1.084	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/N	0.9744	likely_pathogenic	0.9803	pathogenic	-0.997	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9997	pathogenic	0.092	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/Q	0.7406	likely_pathogenic	0.786	pathogenic	-0.673	Destabilizing	1.0	D	0.771	deleterious	N	0.475318804	None	None	N
E/R	0.9748	likely_pathogenic	0.9814	pathogenic	-0.632	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/S	0.9017	likely_pathogenic	0.9202	pathogenic	-1.565	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
E/T	0.9428	likely_pathogenic	0.9592	pathogenic	-1.163	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/V	0.9213	likely_pathogenic	0.9479	pathogenic	0.092	Stabilizing	1.0	D	0.736	prob.delet.	N	0.50056631	None	None	N
E/W	0.9979	likely_pathogenic	0.9982	pathogenic	-0.507	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/Y	0.9897	likely_pathogenic	0.992	pathogenic	-0.14	Destabilizing	1.0	D	0.775	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.