TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35144	105655;105656;105657	chr2:178531185;178531184;178531183	chr2:179395912;179395911;179395910
N2AB	33503	100732;100733;100734	chr2:178531185;178531184;178531183	chr2:179395912;179395911;179395910
N2A	32576	97951;97952;97953	chr2:178531185;178531184;178531183	chr2:179395912;179395911;179395910
N2B	26079	78460;78461;78462	chr2:178531185;178531184;178531183	chr2:179395912;179395911;179395910
Novex-1	26204	78835;78836;78837	chr2:178531185;178531184;178531183	chr2:179395912;179395911;179395910
Novex-2	26271	79036;79037;79038	chr2:178531185;178531184;178531183	chr2:179395912;179395911;179395910
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-164
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.634
• 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	rs568472002	0.761	0.963	N	0.475	0.236	0.263612267334	gnomAD-2.1.1	5.7E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	4.24809E-04	None	0	1.56E-05	0
E/K	rs568472002	0.761	0.963	N	0.475	0.236	0.263612267334	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	4.14594E-04	0
E/K	rs568472002	0.761	0.963	N	0.475	0.236	0.263612267334	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs568472002	0.761	0.963	N	0.475	0.236	0.263612267334	gnomAD-4.0.0	3.03598E-05	None	None	None	None	N	None	2.66581E-05	0	None	0	0	None	0	0	6.78033E-06	4.17225E-04	1.60031E-05

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	0.2589	likely_benign	0.336	benign	-0.743	Destabilizing	0.822	D	0.526	neutral	N	0.494249574	None	None	N
E/C	0.9376	likely_pathogenic	0.9559	pathogenic	-0.18	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
E/D	0.16	likely_benign	0.2002	benign	-0.527	Destabilizing	0.006	N	0.195	neutral	N	0.431216816	None	None	N
E/F	0.8524	likely_pathogenic	0.9022	pathogenic	-0.415	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
E/G	0.2643	likely_benign	0.3557	ambiguous	-0.988	Destabilizing	0.822	D	0.559	neutral	N	0.468967127	None	None	N
E/H	0.6662	likely_pathogenic	0.725	pathogenic	-0.322	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	N
E/I	0.6458	likely_pathogenic	0.7579	pathogenic	-0.11	Destabilizing	0.978	D	0.775	deleterious	None	None	None	None	N
E/K	0.2294	likely_benign	0.2772	benign	0.198	Stabilizing	0.963	D	0.475	neutral	N	0.477221251	None	None	N
E/L	0.674	likely_pathogenic	0.7649	pathogenic	-0.11	Destabilizing	0.978	D	0.75	deleterious	None	None	None	None	N
E/M	0.6284	likely_pathogenic	0.7197	pathogenic	0.148	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
E/N	0.3492	ambiguous	0.4149	ambiguous	-0.333	Destabilizing	0.915	D	0.585	neutral	None	None	None	None	N
E/P	0.9556	likely_pathogenic	0.9722	pathogenic	-0.301	Destabilizing	0.978	D	0.637	neutral	None	None	None	None	N
E/Q	0.1925	likely_benign	0.2154	benign	-0.266	Destabilizing	0.976	D	0.591	neutral	N	0.441145808	None	None	N
E/R	0.41	ambiguous	0.4685	ambiguous	0.397	Stabilizing	0.978	D	0.625	neutral	None	None	None	None	N
E/S	0.2885	likely_benign	0.3646	ambiguous	-0.486	Destabilizing	0.86	D	0.48	neutral	None	None	None	None	N
E/T	0.3869	ambiguous	0.4852	ambiguous	-0.272	Destabilizing	0.956	D	0.595	neutral	None	None	None	None	N
E/V	0.4145	ambiguous	0.5283	ambiguous	-0.301	Destabilizing	0.971	D	0.685	prob.neutral	N	0.457888295	None	None	N
E/W	0.9564	likely_pathogenic	0.9745	pathogenic	-0.141	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
E/Y	0.7715	likely_pathogenic	0.8424	pathogenic	-0.14	Destabilizing	0.998	D	0.708	prob.delet.	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.