TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22122	66589;66590;66591	chr2:178582005;178582004;178582003	chr2:179446732;179446731;179446730
N2AB	20481	61666;61667;61668	chr2:178582005;178582004;178582003	chr2:179446732;179446731;179446730
N2A	19554	58885;58886;58887	chr2:178582005;178582004;178582003	chr2:179446732;179446731;179446730
N2B	13057	39394;39395;39396	chr2:178582005;178582004;178582003	chr2:179446732;179446731;179446730
Novex-1	13182	39769;39770;39771	chr2:178582005;178582004;178582003	chr2:179446732;179446731;179446730
Novex-2	13249	39970;39971;39972	chr2:178582005;178582004;178582003	chr2:179446732;179446731;179446730
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: Fn3-48
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.5741
• 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	rs764747244	0.522	0.919	N	0.563	0.295	0.37568098594	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
E/K	rs764747244	0.522	0.919	N	0.563	0.295	0.37568098594	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/K	rs764747244	0.522	0.919	N	0.563	0.295	0.37568098594	gnomAD-4.0.0	1.0538E-05	None	None	None	None	N	None	0	5.00334E-05	None	0	2.23294E-05	None	0	0	1.01737E-05	0	1.60174E-05
E/Q	rs764747244	None	0.414	N	0.303	0.217	0.343334270461	gnomAD-4.0.0	6.84386E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73671E-04	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	0.2662	likely_benign	0.3353	benign	-0.416	Destabilizing	0.958	D	0.587	neutral	D	0.52313526	None	None	N
E/C	0.9441	likely_pathogenic	0.9677	pathogenic	0.014	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/D	0.306	likely_benign	0.3415	ambiguous	-0.395	Destabilizing	0.958	D	0.507	neutral	N	0.494209981	None	None	N
E/F	0.9499	likely_pathogenic	0.9727	pathogenic	-0.344	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/G	0.4977	ambiguous	0.6099	pathogenic	-0.616	Destabilizing	0.988	D	0.634	neutral	N	0.49446347	None	None	N
E/H	0.8415	likely_pathogenic	0.8955	pathogenic	-0.192	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
E/I	0.6036	likely_pathogenic	0.7057	pathogenic	0.074	Stabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
E/K	0.4438	ambiguous	0.5447	ambiguous	0.339	Stabilizing	0.919	D	0.563	neutral	N	0.470318828	None	None	N
E/L	0.7563	likely_pathogenic	0.8457	pathogenic	0.074	Stabilizing	0.991	D	0.682	prob.neutral	None	None	None	None	N
E/M	0.7527	likely_pathogenic	0.8302	pathogenic	0.233	Stabilizing	0.999	D	0.657	neutral	None	None	None	None	N
E/N	0.5716	likely_pathogenic	0.6427	pathogenic	0.026	Stabilizing	0.991	D	0.674	neutral	None	None	None	None	N
E/P	0.5566	ambiguous	0.6131	pathogenic	-0.069	Destabilizing	0.995	D	0.641	neutral	None	None	None	None	N
E/Q	0.3411	ambiguous	0.4171	ambiguous	0.053	Stabilizing	0.414	N	0.303	neutral	N	0.469420228	None	None	N
E/R	0.6173	likely_pathogenic	0.7058	pathogenic	0.491	Stabilizing	0.982	D	0.675	prob.neutral	None	None	None	None	N
E/S	0.4782	ambiguous	0.567	pathogenic	-0.13	Destabilizing	0.968	D	0.629	neutral	None	None	None	None	N
E/T	0.4792	ambiguous	0.5839	pathogenic	0.033	Stabilizing	0.991	D	0.647	neutral	None	None	None	None	N
E/V	0.4199	ambiguous	0.5186	ambiguous	-0.069	Destabilizing	0.988	D	0.657	neutral	N	0.499641257	None	None	N
E/W	0.9838	likely_pathogenic	0.991	pathogenic	-0.198	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/Y	0.9069	likely_pathogenic	0.9462	pathogenic	-0.098	Destabilizing	0.998	D	0.689	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.