TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29688	89287;89288;89289	chr2:178554049;178554048;178554047	chr2:179418776;179418775;179418774
N2AB	28047	84364;84365;84366	chr2:178554049;178554048;178554047	chr2:179418776;179418775;179418774
N2A	27120	81583;81584;81585	chr2:178554049;178554048;178554047	chr2:179418776;179418775;179418774
N2B	20623	62092;62093;62094	chr2:178554049;178554048;178554047	chr2:179418776;179418775;179418774
Novex-1	20748	62467;62468;62469	chr2:178554049;178554048;178554047	chr2:179418776;179418775;179418774
Novex-2	20815	62668;62669;62670	chr2:178554049;178554048;178554047	chr2:179418776;179418775;179418774
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-104
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0961
• 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	rs748577989	-0.738	0.993	N	0.422	0.245	0.54626238531	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
I/L	rs748577989	-0.738	0.993	N	0.422	0.245	0.54626238531	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/L	rs748577989	-0.738	0.993	N	0.422	0.245	0.54626238531	gnomAD-4.0.0	5.124E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.57112E-06	0	0
I/N	rs1559224502	None	1.0	N	0.737	0.474	0.803802688793	gnomAD-4.0.0	6.15786E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49723E-06	3.47818E-05	1.65651E-05
I/T	rs1559224502	None	1.0	N	0.642	0.451	0.669533849121	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.79E-05	None	0	0	None	0	None	0	0	0
I/T	rs1559224502	None	1.0	N	0.642	0.451	0.669533849121	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	4.47207E-05	None	0	0	None	0	0	0	0	0
I/V	rs748577989	None	0.993	N	0.405	0.173	0.522290170867	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs748577989	None	0.993	N	0.405	0.173	0.522290170867	gnomAD-4.0.0	2.562E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78556E-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
I/A	0.7136	likely_pathogenic	0.7784	pathogenic	-2.225	Highly Destabilizing	0.999	D	0.502	neutral	None	None	None	None	N
I/C	0.836	likely_pathogenic	0.8687	pathogenic	-1.346	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
I/D	0.9876	likely_pathogenic	0.993	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
I/E	0.9684	likely_pathogenic	0.9783	pathogenic	-1.858	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
I/F	0.5511	ambiguous	0.6192	pathogenic	-1.201	Destabilizing	1.0	D	0.675	neutral	N	0.47834377	None	None	N
I/G	0.9351	likely_pathogenic	0.9582	pathogenic	-2.76	Highly Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
I/H	0.9454	likely_pathogenic	0.9643	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
I/K	0.9371	likely_pathogenic	0.9558	pathogenic	-1.545	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
I/L	0.1917	likely_benign	0.2083	benign	-0.697	Destabilizing	0.993	D	0.422	neutral	N	0.513456984	None	None	N
I/M	0.2426	likely_benign	0.2677	benign	-0.616	Destabilizing	1.0	D	0.711	prob.delet.	N	0.48788965	None	None	N
I/N	0.8245	likely_pathogenic	0.8706	pathogenic	-1.782	Destabilizing	1.0	D	0.737	prob.delet.	N	0.466009506	None	None	N
I/P	0.9645	likely_pathogenic	0.9799	pathogenic	-1.185	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
I/Q	0.9179	likely_pathogenic	0.9376	pathogenic	-1.656	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
I/R	0.9065	likely_pathogenic	0.9347	pathogenic	-1.304	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
I/S	0.7578	likely_pathogenic	0.8189	pathogenic	-2.531	Highly Destabilizing	1.0	D	0.632	neutral	N	0.506664298	None	None	N
I/T	0.6771	likely_pathogenic	0.7261	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.642	neutral	N	0.511456829	None	None	N
I/V	0.0832	likely_benign	0.0861	benign	-1.185	Destabilizing	0.993	D	0.405	neutral	N	0.399576905	None	None	N
I/W	0.9728	likely_pathogenic	0.9825	pathogenic	-1.533	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
I/Y	0.9279	likely_pathogenic	0.9494	pathogenic	-1.228	Destabilizing	1.0	D	0.678	prob.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.