TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5959	18100;18101;18102	chr2:178730658;178730657;178730656	chr2:179595385;179595384;179595383
N2AB	5642	17149;17150;17151	chr2:178730658;178730657;178730656	chr2:179595385;179595384;179595383
N2A	4715	14368;14369;14370	chr2:178730658;178730657;178730656	chr2:179595385;179595384;179595383
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-43
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1113
• 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/M	rs576711300	-0.259	0.911	N	0.403	0.376	0.566010919861	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
I/M	rs576711300	-0.259	0.911	N	0.403	0.376	0.566010919861	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
I/M	rs576711300	-0.259	0.911	N	0.403	0.376	0.566010919861	gnomAD-4.0.0	3.84328E-06	None	None	None	None	N	None	0	1.69457E-05	None	0	0	None	0	0	4.78698E-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	0.9576	likely_pathogenic	0.9298	pathogenic	-1.798	Destabilizing	0.985	D	0.524	neutral	None	None	None	None	N
I/C	0.9785	likely_pathogenic	0.961	pathogenic	-0.962	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
I/D	0.9964	likely_pathogenic	0.994	pathogenic	-2.474	Highly Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
I/E	0.9917	likely_pathogenic	0.9869	pathogenic	-2.182	Highly Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
I/F	0.5845	likely_pathogenic	0.4848	ambiguous	-1.142	Destabilizing	0.998	D	0.522	neutral	None	None	None	None	N
I/G	0.9909	likely_pathogenic	0.9838	pathogenic	-2.34	Highly Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
I/H	0.9875	likely_pathogenic	0.9776	pathogenic	-2.185	Highly Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
I/K	0.9737	likely_pathogenic	0.9615	pathogenic	-1.237	Destabilizing	0.997	D	0.702	prob.neutral	D	0.561813695	None	None	N
I/L	0.1587	likely_benign	0.1245	benign	-0.195	Destabilizing	0.817	D	0.368	neutral	N	0.504424574	None	None	N
I/M	0.2667	likely_benign	0.2246	benign	-0.281	Destabilizing	0.911	D	0.403	neutral	N	0.507309893	None	None	N
I/N	0.9649	likely_pathogenic	0.945	pathogenic	-1.873	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
I/P	0.9924	likely_pathogenic	0.9876	pathogenic	-0.717	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
I/Q	0.9832	likely_pathogenic	0.9722	pathogenic	-1.528	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
I/R	0.9677	likely_pathogenic	0.9496	pathogenic	-1.495	Destabilizing	0.997	D	0.745	deleterious	D	0.561813695	None	None	N
I/S	0.9801	likely_pathogenic	0.9653	pathogenic	-2.384	Highly Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
I/T	0.9612	likely_pathogenic	0.9391	pathogenic	-1.929	Destabilizing	0.98	D	0.568	neutral	D	0.53605921	None	None	N
I/V	0.2004	likely_benign	0.1682	benign	-0.717	Destabilizing	0.219	N	0.201	neutral	N	0.510086684	None	None	N
I/W	0.9859	likely_pathogenic	0.9751	pathogenic	-1.547	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
I/Y	0.9388	likely_pathogenic	0.9005	pathogenic	-1.181	Destabilizing	0.999	D	0.667	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.