TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29075	87448;87449;87450	chr2:178558131;178558130;178558129	chr2:179422858;179422857;179422856
N2AB	27434	82525;82526;82527	chr2:178558131;178558130;178558129	chr2:179422858;179422857;179422856
N2A	26507	79744;79745;79746	chr2:178558131;178558130;178558129	chr2:179422858;179422857;179422856
N2B	20010	60253;60254;60255	chr2:178558131;178558130;178558129	chr2:179422858;179422857;179422856
Novex-1	20135	60628;60629;60630	chr2:178558131;178558130;178558129	chr2:179422858;179422857;179422856
Novex-2	20202	60829;60830;60831	chr2:178558131;178558130;178558129	chr2:179422858;179422857;179422856
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-145
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.8554
• 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/Q	rs1324821269	0.391	1.0	N	0.744	0.412	0.38242337071	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/Q	rs1324821269	0.391	1.0	N	0.744	0.412	0.38242337071	gnomAD-4.0.0	1.59117E-06	None	None	None	None	I	None	0	2.28645E-05	None	0	0	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	0.225	likely_benign	0.1914	benign	0.066	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
K/C	0.6033	likely_pathogenic	0.5073	ambiguous	-0.245	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
K/D	0.5236	ambiguous	0.4475	ambiguous	-0.052	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
K/E	0.1584	likely_benign	0.1346	benign	-0.036	Destabilizing	0.999	D	0.663	neutral	N	0.488439188	None	None	I
K/F	0.7362	likely_pathogenic	0.6493	pathogenic	-0.083	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
K/G	0.412	ambiguous	0.3417	ambiguous	-0.143	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
K/H	0.2592	likely_benign	0.2184	benign	-0.357	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
K/I	0.298	likely_benign	0.2546	benign	0.542	Stabilizing	1.0	D	0.763	deleterious	D	0.530982031	None	None	I
K/L	0.3144	likely_benign	0.262	benign	0.542	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	I
K/M	0.2245	likely_benign	0.1849	benign	0.187	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
K/N	0.3584	ambiguous	0.2938	benign	0.128	Stabilizing	1.0	D	0.757	deleterious	N	0.485985953	None	None	I
K/P	0.8574	likely_pathogenic	0.8056	pathogenic	0.411	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
K/Q	0.121	likely_benign	0.1083	benign	-0.007	Destabilizing	1.0	D	0.744	deleterious	N	0.510662687	None	None	I
K/R	0.0778	likely_benign	0.0732	benign	-0.084	Destabilizing	0.999	D	0.615	neutral	N	0.507219737	None	None	I
K/S	0.2988	likely_benign	0.2492	benign	-0.301	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/T	0.1244	likely_benign	0.1096	benign	-0.138	Destabilizing	1.0	D	0.728	prob.delet.	N	0.438109155	None	None	I
K/V	0.2172	likely_benign	0.1876	benign	0.411	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
K/W	0.7747	likely_pathogenic	0.6705	pathogenic	-0.131	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
K/Y	0.614	likely_pathogenic	0.5114	ambiguous	0.219	Stabilizing	1.0	D	0.751	deleterious	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.