TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18160	54703;54704;54705	chr2:178604209;178604208;178604207	chr2:179468936;179468935;179468934
N2AB	16519	49780;49781;49782	chr2:178604209;178604208;178604207	chr2:179468936;179468935;179468934
N2A	15592	46999;47000;47001	chr2:178604209;178604208;178604207	chr2:179468936;179468935;179468934
N2B	9095	27508;27509;27510	chr2:178604209;178604208;178604207	chr2:179468936;179468935;179468934
Novex-1	9220	27883;27884;27885	chr2:178604209;178604208;178604207	chr2:179468936;179468935;179468934
Novex-2	9287	28084;28085;28086	chr2:178604209;178604208;178604207	chr2:179468936;179468935;179468934
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-19
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.101
• 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
I/L	None	None	None	N	0.227	0.068	0.371157983038	gnomAD-4.0.0	1.59767E-06	None	None	None	None	N	None	0	0	None	0	2.78738E-05	None	0	0	0	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
I/A	0.7648	likely_pathogenic	0.8191	pathogenic	-2.999	Highly Destabilizing	0.002	N	0.475	neutral	None	None	None	None	N
I/C	0.8792	likely_pathogenic	0.8924	pathogenic	-2.469	Highly Destabilizing	0.934	D	0.754	deleterious	None	None	None	None	N
I/D	0.9973	likely_pathogenic	0.9978	pathogenic	-3.65	Highly Destabilizing	0.552	D	0.867	deleterious	None	None	None	None	N
I/E	0.9927	likely_pathogenic	0.994	pathogenic	-3.407	Highly Destabilizing	0.552	D	0.833	deleterious	None	None	None	None	N
I/F	0.5912	likely_pathogenic	0.5927	pathogenic	-1.592	Destabilizing	0.186	N	0.748	deleterious	N	0.483112647	None	None	N
I/G	0.9763	likely_pathogenic	0.9818	pathogenic	-3.503	Highly Destabilizing	0.378	N	0.81	deleterious	None	None	None	None	N
I/H	0.9857	likely_pathogenic	0.9873	pathogenic	-2.855	Highly Destabilizing	0.934	D	0.841	deleterious	None	None	None	None	N
I/K	0.9847	likely_pathogenic	0.9847	pathogenic	-2.281	Highly Destabilizing	0.552	D	0.833	deleterious	None	None	None	None	N
I/L	0.1748	likely_benign	0.1524	benign	-1.503	Destabilizing	None	N	0.227	neutral	N	0.41546629	None	None	N
I/M	0.2444	likely_benign	0.2839	benign	-1.786	Destabilizing	0.186	N	0.751	deleterious	N	0.461393368	None	None	N
I/N	0.9429	likely_pathogenic	0.9527	pathogenic	-2.759	Highly Destabilizing	0.739	D	0.854	deleterious	N	0.472201251	None	None	N
I/P	0.953	likely_pathogenic	0.9645	pathogenic	-1.991	Destabilizing	0.552	D	0.864	deleterious	None	None	None	None	N
I/Q	0.9767	likely_pathogenic	0.9807	pathogenic	-2.564	Highly Destabilizing	0.789	D	0.849	deleterious	None	None	None	None	N
I/R	0.9702	likely_pathogenic	0.9708	pathogenic	-2.008	Highly Destabilizing	0.552	D	0.865	deleterious	None	None	None	None	N
I/S	0.8941	likely_pathogenic	0.9207	pathogenic	-3.33	Highly Destabilizing	0.061	N	0.771	deleterious	N	0.507568375	None	None	N
I/T	0.8377	likely_pathogenic	0.859	pathogenic	-2.959	Highly Destabilizing	0.115	N	0.751	deleterious	N	0.418506595	None	None	N
I/V	0.1757	likely_benign	0.1894	benign	-1.991	Destabilizing	0.012	N	0.618	neutral	N	0.446439771	None	None	N
I/W	0.9908	likely_pathogenic	0.9891	pathogenic	-1.981	Destabilizing	0.934	D	0.819	deleterious	None	None	None	None	N
I/Y	0.9652	likely_pathogenic	0.965	pathogenic	-1.858	Destabilizing	0.552	D	0.778	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.