TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31403	94432;94433;94434	chr2:178547419;178547418;178547417	chr2:179412146;179412145;179412144
N2AB	29762	89509;89510;89511	chr2:178547419;178547418;178547417	chr2:179412146;179412145;179412144
N2A	28835	86728;86729;86730	chr2:178547419;178547418;178547417	chr2:179412146;179412145;179412144
N2B	22338	67237;67238;67239	chr2:178547419;178547418;178547417	chr2:179412146;179412145;179412144
Novex-1	22463	67612;67613;67614	chr2:178547419;178547418;178547417	chr2:179412146;179412145;179412144
Novex-2	22530	67813;67814;67815	chr2:178547419;178547418;178547417	chr2:179412146;179412145;179412144
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: Fn3-116
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.337
• 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	rs746139438	-0.821	0.603	N	0.229	0.279	0.207176502487	gnomAD-2.1.1	8.47E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.88E-05	0
E/K	rs746139438	-0.821	0.603	N	0.229	0.279	0.207176502487	gnomAD-4.0.0	2.76615E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.62935E-06	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	0.23	likely_benign	0.2904	benign	-0.925	Destabilizing	0.991	D	0.454	neutral	N	0.461833298	None	None	N
E/C	0.895	likely_pathogenic	0.9256	pathogenic	-0.645	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/D	0.4162	ambiguous	0.5109	ambiguous	-1.217	Destabilizing	0.996	D	0.385	neutral	N	0.451925736	None	None	N
E/F	0.9167	likely_pathogenic	0.9495	pathogenic	-0.2	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
E/G	0.3635	ambiguous	0.4447	ambiguous	-1.331	Destabilizing	0.999	D	0.541	neutral	N	0.46270009	None	None	N
E/H	0.6856	likely_pathogenic	0.782	pathogenic	-0.623	Destabilizing	1.0	D	0.592	neutral	None	None	None	None	N
E/I	0.5828	likely_pathogenic	0.6799	pathogenic	0.204	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
E/K	0.1979	likely_benign	0.2876	benign	-1.176	Destabilizing	0.603	D	0.229	neutral	N	0.338677588	None	None	N
E/L	0.6358	likely_pathogenic	0.7379	pathogenic	0.204	Stabilizing	0.999	D	0.699	prob.delet.	None	None	None	None	N
E/M	0.6017	likely_pathogenic	0.6987	pathogenic	0.719	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/N	0.5144	ambiguous	0.6385	pathogenic	-1.57	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
E/P	0.9793	likely_pathogenic	0.9858	pathogenic	-0.152	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/Q	0.1319	likely_benign	0.1667	benign	-1.356	Destabilizing	0.991	D	0.567	neutral	N	0.409057606	None	None	N
E/R	0.3376	likely_benign	0.4392	ambiguous	-0.862	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	N
E/S	0.2925	likely_benign	0.3738	ambiguous	-1.953	Destabilizing	0.993	D	0.517	neutral	None	None	None	None	N
E/T	0.3655	ambiguous	0.4573	ambiguous	-1.618	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
E/V	0.3548	ambiguous	0.4448	ambiguous	-0.152	Destabilizing	0.999	D	0.688	prob.delet.	N	0.46165994	None	None	N
E/W	0.9775	likely_pathogenic	0.9849	pathogenic	0.005	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/Y	0.8621	likely_pathogenic	0.9096	pathogenic	-0.003	Destabilizing	1.0	D	0.772	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.