TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21697	65314;65315;65316	chr2:178584462;178584461;178584460	chr2:179449189;179449188;179449187
N2AB	20056	60391;60392;60393	chr2:178584462;178584461;178584460	chr2:179449189;179449188;179449187
N2A	19129	57610;57611;57612	chr2:178584462;178584461;178584460	chr2:179449189;179449188;179449187
N2B	12632	38119;38120;38121	chr2:178584462;178584461;178584460	chr2:179449189;179449188;179449187
Novex-1	12757	38494;38495;38496	chr2:178584462;178584461;178584460	chr2:179449189;179449188;179449187
Novex-2	12824	38695;38696;38697	chr2:178584462;178584461;178584460	chr2:179449189;179449188;179449187
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: Fn3-45
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0974
• 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	rs1469687198	None	1.0	D	0.757	0.531	0.52971305234	gnomAD-4.0.0	1.59232E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	0
E/K	None	None	0.999	N	0.684	0.505	0.462374447365	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9204	likely_pathogenic	0.9312	pathogenic	-0.638	Destabilizing	0.999	D	0.703	prob.neutral	D	0.528937233	None	None	N
E/C	0.9916	likely_pathogenic	0.9915	pathogenic	-0.087	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/D	0.8234	likely_pathogenic	0.9085	pathogenic	-1.595	Destabilizing	0.999	D	0.66	neutral	N	0.487057184	None	None	N
E/F	0.994	likely_pathogenic	0.9947	pathogenic	-0.317	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/G	0.9401	likely_pathogenic	0.9575	pathogenic	-1.049	Destabilizing	1.0	D	0.757	deleterious	D	0.524128295	None	None	N
E/H	0.9736	likely_pathogenic	0.9795	pathogenic	-0.328	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/I	0.9871	likely_pathogenic	0.9879	pathogenic	0.53	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/K	0.9501	likely_pathogenic	0.9623	pathogenic	-0.853	Destabilizing	0.999	D	0.684	prob.neutral	N	0.512692629	None	None	N
E/L	0.9799	likely_pathogenic	0.9824	pathogenic	0.53	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/M	0.98	likely_pathogenic	0.9828	pathogenic	1.126	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/N	0.9798	likely_pathogenic	0.9887	pathogenic	-1.234	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9997	pathogenic	0.158	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Q	0.6804	likely_pathogenic	0.6889	pathogenic	-0.887	Destabilizing	1.0	D	0.754	deleterious	N	0.487662614	None	None	N
E/R	0.9598	likely_pathogenic	0.9677	pathogenic	-0.848	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/S	0.9298	likely_pathogenic	0.9481	pathogenic	-1.739	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
E/T	0.9767	likely_pathogenic	0.98	pathogenic	-1.349	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/V	0.9632	likely_pathogenic	0.9654	pathogenic	0.158	Stabilizing	1.0	D	0.753	deleterious	N	0.511593447	None	None	N
E/W	0.997	likely_pathogenic	0.9976	pathogenic	-0.532	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/Y	0.9904	likely_pathogenic	0.9922	pathogenic	-0.14	Destabilizing	1.0	D	0.795	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.