TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1612	5059;5060;5061	chr2:178777030;178777029;178777028	chr2:179641757;179641756;179641755
N2AB	1612	5059;5060;5061	chr2:178777030;178777029;178777028	chr2:179641757;179641756;179641755
N2A	1612	5059;5060;5061	chr2:178777030;178777029;178777028	chr2:179641757;179641756;179641755
N2B	1566	4921;4922;4923	chr2:178777030;178777029;178777028	chr2:179641757;179641756;179641755
Novex-1	1566	4921;4922;4923	chr2:178777030;178777029;178777028	chr2:179641757;179641756;179641755
Novex-2	1566	4921;4922;4923	chr2:178777030;178777029;178777028	chr2:179641757;179641756;179641755
Novex-3	1612	5059;5060;5061	chr2:178777030;178777029;178777028	chr2:179641757;179641756;179641755

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-7
• Domain position: 57
• Structural Position: 135
• Q(SASA): 0.312
• 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	rs1445985420	0.259	0.062	N	0.448	0.339	0.226586394389	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	8.68E-05	None	0	0	None	0	None	0	0	0
E/K	rs1445985420	0.259	0.062	N	0.448	0.339	0.226586394389	gnomAD-3.1.2	7.88E-05	None	None	None	None	N	None	0	7.85443E-04	0	0	0	None	0	0	0	0	0
E/K	rs1445985420	0.259	0.062	N	0.448	0.339	0.226586394389	gnomAD-4.0.0	2.17728E-05	None	None	None	None	N	None	0	2.88116E-04	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	0.2189	likely_benign	0.163	benign	-0.583	Destabilizing	None	N	0.327	neutral	N	0.475255255	None	None	N
E/C	0.9179	likely_pathogenic	0.8554	pathogenic	0.041	Stabilizing	0.935	D	0.726	prob.delet.	None	None	None	None	N
E/D	0.2359	likely_benign	0.2061	benign	-0.66	Destabilizing	0.117	N	0.423	neutral	N	0.50268043	None	None	N
E/F	0.7328	likely_pathogenic	0.6398	pathogenic	-0.61	Destabilizing	0.235	N	0.735	prob.delet.	None	None	None	None	N
E/G	0.378	ambiguous	0.2899	benign	-0.818	Destabilizing	0.062	N	0.631	neutral	N	0.465616644	None	None	N
E/H	0.6042	likely_pathogenic	0.4938	ambiguous	-0.748	Destabilizing	0.555	D	0.503	neutral	None	None	None	None	N
E/I	0.3276	likely_benign	0.2483	benign	0.016	Stabilizing	0.235	N	0.677	prob.neutral	None	None	None	None	N
E/K	0.26	likely_benign	0.1875	benign	0.174	Stabilizing	0.062	N	0.448	neutral	N	0.485155052	None	None	N
E/L	0.4637	ambiguous	0.3616	ambiguous	0.016	Stabilizing	0.001	N	0.485	neutral	None	None	None	None	N
E/M	0.4385	ambiguous	0.347	ambiguous	0.389	Stabilizing	0.235	N	0.693	prob.neutral	None	None	None	None	N
E/N	0.3798	ambiguous	0.3044	benign	-0.115	Destabilizing	0.38	N	0.481	neutral	None	None	None	None	N
E/P	0.9841	likely_pathogenic	0.9749	pathogenic	-0.163	Destabilizing	0.555	D	0.622	neutral	None	None	None	None	N
E/Q	0.1903	likely_benign	0.1508	benign	-0.1	Destabilizing	0.002	N	0.179	neutral	N	0.462288111	None	None	N
E/R	0.465	ambiguous	0.349	ambiguous	0.214	Stabilizing	0.235	N	0.48	neutral	None	None	None	None	N
E/S	0.2931	likely_benign	0.2284	benign	-0.306	Destabilizing	0.081	N	0.435	neutral	None	None	None	None	N
E/T	0.2843	likely_benign	0.2177	benign	-0.115	Destabilizing	0.149	N	0.538	neutral	None	None	None	None	N
E/V	0.2008	likely_benign	0.1544	benign	-0.163	Destabilizing	0.062	N	0.619	neutral	N	0.463774308	None	None	N
E/W	0.9388	likely_pathogenic	0.8933	pathogenic	-0.481	Destabilizing	0.935	D	0.737	prob.delet.	None	None	None	None	N
E/Y	0.6947	likely_pathogenic	0.5921	pathogenic	-0.36	Destabilizing	0.555	D	0.703	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.