TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29106	87541;87542;87543	chr2:178558038;178558037;178558036	chr2:179422765;179422764;179422763
N2AB	27465	82618;82619;82620	chr2:178558038;178558037;178558036	chr2:179422765;179422764;179422763
N2A	26538	79837;79838;79839	chr2:178558038;178558037;178558036	chr2:179422765;179422764;179422763
N2B	20041	60346;60347;60348	chr2:178558038;178558037;178558036	chr2:179422765;179422764;179422763
Novex-1	20166	60721;60722;60723	chr2:178558038;178558037;178558036	chr2:179422765;179422764;179422763
Novex-2	20233	60922;60923;60924	chr2:178558038;178558037;178558036	chr2:179422765;179422764;179422763
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: Ig-145
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.5725
• 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/G	rs1559263086	None	0.892	N	0.541	0.307	0.29132392195	gnomAD-4.0.0	1.59101E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85776E-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	0.4321	ambiguous	0.5672	pathogenic	-0.639	Destabilizing	0.892	D	0.557	neutral	N	0.49920989	None	None	N
E/C	0.961	likely_pathogenic	0.9789	pathogenic	-0.055	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
E/D	0.1203	likely_benign	0.1657	benign	-0.446	Destabilizing	0.011	N	0.181	neutral	N	0.428808442	None	None	N
E/F	0.9406	likely_pathogenic	0.9692	pathogenic	-0.523	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/G	0.3456	ambiguous	0.4578	ambiguous	-0.86	Destabilizing	0.892	D	0.541	neutral	N	0.476063671	None	None	N
E/H	0.8386	likely_pathogenic	0.904	pathogenic	-0.5	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
E/I	0.8436	likely_pathogenic	0.9081	pathogenic	-0.078	Destabilizing	0.987	D	0.772	deleterious	None	None	None	None	N
E/K	0.607	likely_pathogenic	0.7227	pathogenic	0.178	Stabilizing	0.892	D	0.505	neutral	N	0.451050583	None	None	N
E/L	0.8241	likely_pathogenic	0.9043	pathogenic	-0.078	Destabilizing	0.987	D	0.745	deleterious	None	None	None	None	N
E/M	0.8332	likely_pathogenic	0.9035	pathogenic	0.235	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
E/N	0.4169	ambiguous	0.5711	pathogenic	-0.163	Destabilizing	0.95	D	0.585	neutral	None	None	None	None	N
E/P	0.9539	likely_pathogenic	0.9736	pathogenic	-0.245	Destabilizing	0.987	D	0.667	neutral	None	None	None	None	N
E/Q	0.429	ambiguous	0.5207	ambiguous	-0.125	Destabilizing	0.983	D	0.575	neutral	N	0.4918412	None	None	N
E/R	0.7443	likely_pathogenic	0.8324	pathogenic	0.312	Stabilizing	0.987	D	0.628	neutral	None	None	None	None	N
E/S	0.4732	ambiguous	0.6152	pathogenic	-0.349	Destabilizing	0.916	D	0.515	neutral	None	None	None	None	N
E/T	0.6369	likely_pathogenic	0.7599	pathogenic	-0.163	Destabilizing	0.975	D	0.608	neutral	None	None	None	None	N
E/V	0.6555	likely_pathogenic	0.7626	pathogenic	-0.245	Destabilizing	0.983	D	0.697	prob.neutral	N	0.492534633	None	None	N
E/W	0.9773	likely_pathogenic	0.9884	pathogenic	-0.338	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/Y	0.8204	likely_pathogenic	0.8991	pathogenic	-0.276	Destabilizing	0.999	D	0.707	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.