TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21182	63769;63770;63771	chr2:178587765;178587764;178587763	chr2:179452492;179452491;179452490
N2AB	19541	58846;58847;58848	chr2:178587765;178587764;178587763	chr2:179452492;179452491;179452490
N2A	18614	56065;56066;56067	chr2:178587765;178587764;178587763	chr2:179452492;179452491;179452490
N2B	12117	36574;36575;36576	chr2:178587765;178587764;178587763	chr2:179452492;179452491;179452490
Novex-1	12242	36949;36950;36951	chr2:178587765;178587764;178587763	chr2:179452492;179452491;179452490
Novex-2	12309	37150;37151;37152	chr2:178587765;178587764;178587763	chr2:179452492;179452491;179452490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-123
• Domain position: 6
• Structural Position: 9
• Q(SASA): 0.8578
• Predicted PPI site: I

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
K/E	rs565176987	0.249	0.067	D	0.346	0.22	0.266385636622	gnomAD-2.1.1	7.27E-06	None	None	None	None	I	None	0	0	None	0	1.03821E-04	None	0	None	0	0	0
K/E	rs565176987	0.249	0.067	D	0.346	0.22	0.266385636622	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	5.81621E-04	None	0	0	0	0	0
K/E	rs565176987	0.249	0.067	D	0.346	0.22	0.266385636622	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
K/E	rs565176987	0.249	0.067	D	0.346	0.22	0.266385636622	gnomAD-4.0.0	6.46277E-06	None	None	None	None	I	None	0	0	None	0	1.22124E-04	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
K/A	0.7859	likely_pathogenic	0.7662	pathogenic	0.024	Stabilizing	0.968	D	0.606	neutral	None	None	None	None	I
K/C	0.9182	likely_pathogenic	0.9139	pathogenic	-0.296	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/D	0.7641	likely_pathogenic	0.7231	pathogenic	0.103	Stabilizing	0.938	D	0.62	neutral	None	None	None	None	I
K/E	0.5737	likely_pathogenic	0.5053	ambiguous	0.11	Stabilizing	0.067	N	0.346	neutral	D	0.529899022	None	None	I
K/F	0.9819	likely_pathogenic	0.9782	pathogenic	-0.209	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
K/G	0.7063	likely_pathogenic	0.6868	pathogenic	-0.161	Destabilizing	0.991	D	0.536	neutral	None	None	None	None	I
K/H	0.524	ambiguous	0.5006	ambiguous	-0.37	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
K/I	0.9105	likely_pathogenic	0.8949	pathogenic	0.427	Stabilizing	0.994	D	0.65	neutral	N	0.507934414	None	None	I
K/L	0.8222	likely_pathogenic	0.8074	pathogenic	0.427	Stabilizing	0.991	D	0.555	neutral	None	None	None	None	I
K/M	0.7467	likely_pathogenic	0.7113	pathogenic	0.141	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	I
K/N	0.6908	likely_pathogenic	0.649	pathogenic	0.142	Stabilizing	0.988	D	0.666	neutral	N	0.484461334	None	None	I
K/P	0.8807	likely_pathogenic	0.8773	pathogenic	0.32	Stabilizing	0.995	D	0.655	neutral	None	None	None	None	I
K/Q	0.2696	likely_benign	0.2588	benign	0.003	Stabilizing	0.976	D	0.649	neutral	N	0.466581049	None	None	I
K/R	0.1119	likely_benign	0.1125	benign	-0.064	Destabilizing	0.958	D	0.629	neutral	N	0.480857068	None	None	I
K/S	0.7348	likely_pathogenic	0.7046	pathogenic	-0.331	Destabilizing	0.968	D	0.661	neutral	None	None	None	None	I
K/T	0.564	likely_pathogenic	0.5255	ambiguous	-0.179	Destabilizing	0.988	D	0.625	neutral	N	0.486409891	None	None	I
K/V	0.8685	likely_pathogenic	0.846	pathogenic	0.32	Stabilizing	0.995	D	0.606	neutral	None	None	None	None	I
K/W	0.9686	likely_pathogenic	0.9645	pathogenic	-0.255	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
K/Y	0.916	likely_pathogenic	0.9004	pathogenic	0.105	Stabilizing	0.998	D	0.615	neutral	None	None	None	None	I

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.