TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31544	94855;94856;94857	chr2:178546798;178546797;178546796	chr2:179411525;179411524;179411523
N2AB	29903	89932;89933;89934	chr2:178546798;178546797;178546796	chr2:179411525;179411524;179411523
N2A	28976	87151;87152;87153	chr2:178546798;178546797;178546796	chr2:179411525;179411524;179411523
N2B	22479	67660;67661;67662	chr2:178546798;178546797;178546796	chr2:179411525;179411524;179411523
Novex-1	22604	68035;68036;68037	chr2:178546798;178546797;178546796	chr2:179411525;179411524;179411523
Novex-2	22671	68236;68237;68238	chr2:178546798;178546797;178546796	chr2:179411525;179411524;179411523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-118
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1249
• 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/Q	rs1024530763	-2.119	1.0	N	0.789	0.415	0.33440975612	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/Q	rs1024530763	-2.119	1.0	N	0.789	0.415	0.33440975612	gnomAD-4.0.0	1.59165E-06	None	None	None	None	N	None	0	2.28686E-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
E/A	0.9701	likely_pathogenic	0.9583	pathogenic	-1.591	Destabilizing	0.999	D	0.721	prob.delet.	D	0.556587368	None	None	N
E/C	0.9936	likely_pathogenic	0.9927	pathogenic	-0.806	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.9587	likely_pathogenic	0.9452	pathogenic	-1.807	Destabilizing	0.999	D	0.719	prob.delet.	N	0.485905095	None	None	N
E/F	0.9973	likely_pathogenic	0.9959	pathogenic	-1.262	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/G	0.9784	likely_pathogenic	0.9717	pathogenic	-1.97	Destabilizing	1.0	D	0.778	deleterious	D	0.54025754	None	None	N
E/H	0.9928	likely_pathogenic	0.9895	pathogenic	-1.15	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/I	0.9931	likely_pathogenic	0.9896	pathogenic	-0.497	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/K	0.9809	likely_pathogenic	0.9734	pathogenic	-1.682	Destabilizing	0.999	D	0.734	prob.delet.	D	0.52585936	None	None	N
E/L	0.9894	likely_pathogenic	0.9839	pathogenic	-0.497	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/M	0.9898	likely_pathogenic	0.9848	pathogenic	0.245	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/N	0.9952	likely_pathogenic	0.9917	pathogenic	-1.887	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.849	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Q	0.8128	likely_pathogenic	0.7512	pathogenic	-1.593	Destabilizing	1.0	D	0.789	deleterious	N	0.485358436	None	None	N
E/R	0.98	likely_pathogenic	0.9761	pathogenic	-1.489	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/S	0.9708	likely_pathogenic	0.9578	pathogenic	-2.495	Highly Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/T	0.9887	likely_pathogenic	0.984	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/V	0.9818	likely_pathogenic	0.9743	pathogenic	-0.849	Destabilizing	1.0	D	0.779	deleterious	D	0.530849791	None	None	N
E/W	0.9984	likely_pathogenic	0.9981	pathogenic	-1.365	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9946	likely_pathogenic	0.9922	pathogenic	-1.102	Destabilizing	1.0	D	0.793	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.