TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21398	64417;64418;64419	chr2:178586709;178586708;178586707	chr2:179451436;179451435;179451434
N2AB	19757	59494;59495;59496	chr2:178586709;178586708;178586707	chr2:179451436;179451435;179451434
N2A	18830	56713;56714;56715	chr2:178586709;178586708;178586707	chr2:179451436;179451435;179451434
N2B	12333	37222;37223;37224	chr2:178586709;178586708;178586707	chr2:179451436;179451435;179451434
Novex-1	12458	37597;37598;37599	chr2:178586709;178586708;178586707	chr2:179451436;179451435;179451434
Novex-2	12525	37798;37799;37800	chr2:178586709;178586708;178586707	chr2:179451436;179451435;179451434
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: Fn3-43
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1782
• 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
I/S	rs727504754	-2.171	0.942	D	0.765	0.52	0.8006517185	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.61455E-04	None	0	0	0
I/S	rs727504754	-2.171	0.942	D	0.765	0.52	0.8006517185	gnomAD-4.0.0	1.75201E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.57652E-04	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	0.9546	likely_pathogenic	0.9435	pathogenic	-2.196	Highly Destabilizing	0.754	D	0.637	neutral	None	None	None	None	I
I/C	0.9895	likely_pathogenic	0.9862	pathogenic	-1.312	Destabilizing	0.994	D	0.699	prob.neutral	None	None	None	None	I
I/D	0.9981	likely_pathogenic	0.9974	pathogenic	-1.971	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	I
I/E	0.9917	likely_pathogenic	0.9891	pathogenic	-1.911	Destabilizing	0.978	D	0.801	deleterious	None	None	None	None	I
I/F	0.9566	likely_pathogenic	0.9443	pathogenic	-1.533	Destabilizing	0.942	D	0.734	prob.delet.	N	0.510382587	None	None	I
I/G	0.9958	likely_pathogenic	0.9942	pathogenic	-2.597	Highly Destabilizing	0.978	D	0.806	deleterious	None	None	None	None	I
I/H	0.9976	likely_pathogenic	0.9966	pathogenic	-1.83	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
I/K	0.9887	likely_pathogenic	0.9848	pathogenic	-1.569	Destabilizing	0.978	D	0.799	deleterious	None	None	None	None	I
I/L	0.6543	likely_pathogenic	0.6048	pathogenic	-1.117	Destabilizing	0.294	N	0.442	neutral	N	0.474654603	None	None	I
I/M	0.6354	likely_pathogenic	0.5725	pathogenic	-0.789	Destabilizing	0.976	D	0.692	prob.neutral	D	0.533490499	None	None	I
I/N	0.9642	likely_pathogenic	0.9474	pathogenic	-1.474	Destabilizing	0.99	D	0.806	deleterious	D	0.523148152	None	None	I
I/P	0.9569	likely_pathogenic	0.9535	pathogenic	-1.45	Destabilizing	0.993	D	0.807	deleterious	None	None	None	None	I
I/Q	0.9923	likely_pathogenic	0.9895	pathogenic	-1.61	Destabilizing	0.993	D	0.8	deleterious	None	None	None	None	I
I/R	0.9843	likely_pathogenic	0.9801	pathogenic	-0.956	Destabilizing	0.978	D	0.809	deleterious	None	None	None	None	I
I/S	0.977	likely_pathogenic	0.968	pathogenic	-2.123	Highly Destabilizing	0.942	D	0.765	deleterious	D	0.526996039	None	None	I
I/T	0.8833	likely_pathogenic	0.8361	pathogenic	-1.94	Destabilizing	0.822	D	0.748	deleterious	N	0.518602248	None	None	I
I/V	0.192	likely_benign	0.1591	benign	-1.45	Destabilizing	0.006	N	0.251	neutral	N	0.491009773	None	None	I
I/W	0.9974	likely_pathogenic	0.9969	pathogenic	-1.701	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	I
I/Y	0.9917	likely_pathogenic	0.9886	pathogenic	-1.482	Destabilizing	0.978	D	0.742	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.