TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16528	49807;49808;49809	chr2:178613227;178613226;178613225	chr2:179477954;179477953;179477952
N2AB	14887	44884;44885;44886	chr2:178613227;178613226;178613225	chr2:179477954;179477953;179477952
N2A	13960	42103;42104;42105	chr2:178613227;178613226;178613225	chr2:179477954;179477953;179477952
N2B	7463	22612;22613;22614	chr2:178613227;178613226;178613225	chr2:179477954;179477953;179477952
Novex-1	7588	22987;22988;22989	chr2:178613227;178613226;178613225	chr2:179477954;179477953;179477952
Novex-2	7655	23188;23189;23190	chr2:178613227;178613226;178613225	chr2:179477954;179477953;179477952
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: Fn3-7
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2148
• 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	0.485	0.396	0.349204839081	gnomAD-4.0.0	6.85133E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00126E-07	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	0.8555	likely_pathogenic	0.7339	pathogenic	-1.167	Destabilizing	0.999	D	0.638	neutral	N	0.464062798	None	None	N
E/C	0.99	likely_pathogenic	0.9719	pathogenic	-0.933	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
E/D	0.9099	likely_pathogenic	0.8775	pathogenic	-1.506	Destabilizing	0.999	D	0.462	neutral	D	0.614839725	None	None	N
E/F	0.995	likely_pathogenic	0.9836	pathogenic	-1.24	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
E/G	0.925	likely_pathogenic	0.8859	pathogenic	-1.535	Destabilizing	1.0	D	0.743	deleterious	D	0.584425016	None	None	N
E/H	0.9846	likely_pathogenic	0.9613	pathogenic	-1.498	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
E/I	0.9088	likely_pathogenic	0.7197	pathogenic	-0.146	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
E/K	0.8895	likely_pathogenic	0.7488	pathogenic	-1.444	Destabilizing	0.999	D	0.485	neutral	N	0.470729637	None	None	N
E/L	0.9634	likely_pathogenic	0.8762	pathogenic	-0.146	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/M	0.9466	likely_pathogenic	0.8191	pathogenic	0.471	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/N	0.9722	likely_pathogenic	0.9469	pathogenic	-1.665	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9992	pathogenic	-0.468	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/Q	0.6555	likely_pathogenic	0.4704	ambiguous	-1.41	Destabilizing	1.0	D	0.587	neutral	N	0.475521385	None	None	N
E/R	0.9446	likely_pathogenic	0.882	pathogenic	-1.392	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/S	0.9089	likely_pathogenic	0.8477	pathogenic	-2.217	Highly Destabilizing	0.999	D	0.518	neutral	None	None	None	None	N
E/T	0.9191	likely_pathogenic	0.8257	pathogenic	-1.881	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/V	0.7947	likely_pathogenic	0.5381	ambiguous	-0.468	Destabilizing	1.0	D	0.802	deleterious	N	0.441534686	None	None	N
E/W	0.9985	likely_pathogenic	0.9956	pathogenic	-1.407	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/Y	0.9926	likely_pathogenic	0.9767	pathogenic	-1.111	Destabilizing	1.0	D	0.84	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.