TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2833	8722;8723;8724	chr2:178770204;178770203;178770202	chr2:179634931;179634930;179634929
N2AB	2833	8722;8723;8724	chr2:178770204;178770203;178770202	chr2:179634931;179634930;179634929
N2A	2833	8722;8723;8724	chr2:178770204;178770203;178770202	chr2:179634931;179634930;179634929
N2B	2787	8584;8585;8586	chr2:178770204;178770203;178770202	chr2:179634931;179634930;179634929
Novex-1	2787	8584;8585;8586	chr2:178770204;178770203;178770202	chr2:179634931;179634930;179634929
Novex-2	2787	8584;8585;8586	chr2:178770204;178770203;178770202	chr2:179634931;179634930;179634929
Novex-3	2833	8722;8723;8724	chr2:178770204;178770203;178770202	chr2:179634931;179634930;179634929

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-18
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.1789
• 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	None	None	0.999	D	0.585	0.582	0.722574115261	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	0.2124	likely_benign	0.2534	benign	-0.494	Destabilizing	0.996	D	0.578	neutral	D	0.553082429	None	None	N
E/C	0.9289	likely_pathogenic	0.9359	pathogenic	-0.454	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/D	0.4435	ambiguous	0.5183	ambiguous	-0.662	Destabilizing	0.998	D	0.476	neutral	D	0.60559257	None	None	N
E/F	0.9293	likely_pathogenic	0.9414	pathogenic	0.199	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/G	0.5157	ambiguous	0.5735	pathogenic	-0.807	Destabilizing	0.999	D	0.585	neutral	D	0.689675643	None	None	N
E/H	0.8335	likely_pathogenic	0.8654	pathogenic	0.389	Stabilizing	1.0	D	0.587	neutral	None	None	None	None	N
E/I	0.4669	ambiguous	0.5164	ambiguous	0.345	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/K	0.3819	ambiguous	0.4268	ambiguous	-0.113	Destabilizing	0.998	D	0.555	neutral	D	0.543370681	None	None	N
E/L	0.5326	ambiguous	0.6015	pathogenic	0.345	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
E/M	0.5556	ambiguous	0.6007	pathogenic	0.353	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
E/N	0.6604	likely_pathogenic	0.7236	pathogenic	-0.776	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
E/P	0.524	ambiguous	0.5722	pathogenic	0.087	Stabilizing	0.504	D	0.327	neutral	None	None	None	None	N
E/Q	0.256	likely_benign	0.2941	benign	-0.639	Destabilizing	1.0	D	0.559	neutral	D	0.55891321	None	None	N
E/R	0.6155	likely_pathogenic	0.6554	pathogenic	0.326	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
E/S	0.4952	ambiguous	0.5691	pathogenic	-0.974	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
E/T	0.4559	ambiguous	0.5194	ambiguous	-0.703	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
E/V	0.2764	likely_benign	0.3059	benign	0.087	Stabilizing	0.999	D	0.633	neutral	N	0.515763998	None	None	N
E/W	0.9846	likely_pathogenic	0.9861	pathogenic	0.484	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/Y	0.9168	likely_pathogenic	0.9281	pathogenic	0.469	Stabilizing	1.0	D	0.649	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.