TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7304	22135;22136;22137	chr2:178723097;178723096;178723095	chr2:179587824;179587823;179587822
N2AB	6987	21184;21185;21186	chr2:178723097;178723096;178723095	chr2:179587824;179587823;179587822
N2A	6060	18403;18404;18405	chr2:178723097;178723096;178723095	chr2:179587824;179587823;179587822
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: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-57
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0548
• 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/T	rs766599708	-2.815	0.324	N	0.739	0.27	0.598985906569	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	1.78E-05	0
I/T	rs766599708	-2.815	0.324	N	0.739	0.27	0.598985906569	gnomAD-4.0.0	4.10583E-06	None	None	None	None	N	None	0	2.23664E-05	None	0	0	None	0	0	4.49779E-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	0.4492	ambiguous	0.4486	ambiguous	-2.976	Highly Destabilizing	0.116	N	0.691	prob.neutral	None	None	None	None	N
I/C	0.9423	likely_pathogenic	0.9488	pathogenic	-2.373	Highly Destabilizing	0.944	D	0.79	deleterious	None	None	None	None	N
I/D	0.9971	likely_pathogenic	0.9964	pathogenic	-3.632	Highly Destabilizing	0.818	D	0.853	deleterious	None	None	None	None	N
I/E	0.99	likely_pathogenic	0.9876	pathogenic	-3.369	Highly Destabilizing	0.818	D	0.835	deleterious	None	None	None	None	N
I/F	0.7809	likely_pathogenic	0.7921	pathogenic	-1.648	Destabilizing	0.627	D	0.76	deleterious	N	0.503863171	None	None	N
I/G	0.9471	likely_pathogenic	0.9471	pathogenic	-3.517	Highly Destabilizing	0.818	D	0.815	deleterious	None	None	None	None	N
I/H	0.9954	likely_pathogenic	0.9949	pathogenic	-2.984	Highly Destabilizing	0.981	D	0.837	deleterious	None	None	None	None	N
I/K	0.9865	likely_pathogenic	0.9829	pathogenic	-2.291	Highly Destabilizing	0.818	D	0.821	deleterious	None	None	None	None	N
I/L	0.261	likely_benign	0.2881	benign	-1.365	Destabilizing	0.001	N	0.285	neutral	N	0.50435279	None	None	N
I/M	0.2504	likely_benign	0.2547	benign	-1.593	Destabilizing	0.627	D	0.712	prob.delet.	N	0.488886015	None	None	N
I/N	0.9656	likely_pathogenic	0.959	pathogenic	-2.799	Highly Destabilizing	0.912	D	0.853	deleterious	N	0.51563755	None	None	N
I/P	0.9915	likely_pathogenic	0.9902	pathogenic	-1.891	Destabilizing	0.932	D	0.856	deleterious	None	None	None	None	N
I/Q	0.987	likely_pathogenic	0.985	pathogenic	-2.577	Highly Destabilizing	0.932	D	0.851	deleterious	None	None	None	None	N
I/R	0.9749	likely_pathogenic	0.9695	pathogenic	-2.061	Highly Destabilizing	0.818	D	0.856	deleterious	None	None	None	None	N
I/S	0.8533	likely_pathogenic	0.8456	pathogenic	-3.391	Highly Destabilizing	0.627	D	0.798	deleterious	N	0.491999887	None	None	N
I/T	0.4597	ambiguous	0.4621	ambiguous	-2.992	Highly Destabilizing	0.324	N	0.739	prob.delet.	N	0.485251937	None	None	N
I/V	0.0783	likely_benign	0.0903	benign	-1.891	Destabilizing	0.001	N	0.259	neutral	N	0.401758779	None	None	N
I/W	0.9945	likely_pathogenic	0.9937	pathogenic	-2.085	Highly Destabilizing	0.981	D	0.827	deleterious	None	None	None	None	N
I/Y	0.9789	likely_pathogenic	0.975	pathogenic	-1.918	Destabilizing	0.818	D	0.809	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.