TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7236	21931;21932;21933	chr2:178723301;178723300;178723299	chr2:179588028;179588027;179588026
N2AB	6919	20980;20981;20982	chr2:178723301;178723300;178723299	chr2:179588028;179588027;179588026
N2A	5992	18199;18200;18201	chr2:178723301;178723300;178723299	chr2:179588028;179588027;179588026
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-57
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1595
• 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
L/I	None	None	0.026	N	0.256	0.136	0.124217242631	gnomAD-4.0.0	6.16289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09903E-06	0	0
L/S	rs746222807	-2.072	0.968	N	0.759	0.397	0.700023067923	gnomAD-2.1.1	2.16E-05	None	None	None	None	N	None	2.48715E-04	0	None	0	0	None	0	None	0	0	0
L/S	rs746222807	-2.072	0.968	N	0.759	0.397	0.700023067923	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	1.44795E-04	0	0	0	0	None	0	0	0	0	0
L/S	rs746222807	-2.072	0.968	N	0.759	0.397	0.700023067923	gnomAD-4.0.0	9.30223E-06	None	None	None	None	N	None	2.00567E-04	0	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
L/A	0.7875	likely_pathogenic	0.8329	pathogenic	-1.747	Destabilizing	0.919	D	0.657	neutral	None	None	None	None	N
L/C	0.8811	likely_pathogenic	0.8907	pathogenic	-1.191	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
L/D	0.9925	likely_pathogenic	0.9931	pathogenic	-0.567	Destabilizing	0.976	D	0.839	deleterious	None	None	None	None	N
L/E	0.9656	likely_pathogenic	0.9686	pathogenic	-0.482	Destabilizing	0.952	D	0.809	deleterious	None	None	None	None	N
L/F	0.4926	ambiguous	0.487	ambiguous	-0.999	Destabilizing	0.059	N	0.456	neutral	N	0.488905792	None	None	N
L/G	0.9536	likely_pathogenic	0.9547	pathogenic	-2.159	Highly Destabilizing	0.988	D	0.827	deleterious	None	None	None	None	N
L/H	0.9287	likely_pathogenic	0.9356	pathogenic	-1.314	Destabilizing	0.997	D	0.819	deleterious	None	None	None	None	N
L/I	0.1608	likely_benign	0.1958	benign	-0.655	Destabilizing	0.026	N	0.256	neutral	N	0.469787579	None	None	N
L/K	0.9552	likely_pathogenic	0.9572	pathogenic	-1.016	Destabilizing	0.952	D	0.759	deleterious	None	None	None	None	N
L/M	0.2434	likely_benign	0.2466	benign	-0.648	Destabilizing	0.976	D	0.649	neutral	None	None	None	None	N
L/N	0.9533	likely_pathogenic	0.956	pathogenic	-0.909	Destabilizing	0.988	D	0.839	deleterious	None	None	None	None	N
L/P	0.4303	ambiguous	0.4957	ambiguous	-0.989	Destabilizing	0.996	D	0.845	deleterious	None	None	None	None	N
L/Q	0.8693	likely_pathogenic	0.8801	pathogenic	-0.936	Destabilizing	0.702	D	0.611	neutral	None	None	None	None	N
L/R	0.9281	likely_pathogenic	0.9365	pathogenic	-0.645	Destabilizing	0.976	D	0.788	deleterious	None	None	None	None	N
L/S	0.939	likely_pathogenic	0.9521	pathogenic	-1.734	Destabilizing	0.968	D	0.759	deleterious	N	0.486525935	None	None	N
L/T	0.8392	likely_pathogenic	0.8767	pathogenic	-1.508	Destabilizing	0.976	D	0.759	deleterious	None	None	None	None	N
L/V	0.2228	likely_benign	0.2813	benign	-0.989	Destabilizing	0.64	D	0.579	neutral	N	0.477042507	None	None	N
L/W	0.8956	likely_pathogenic	0.8976	pathogenic	-1.072	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
L/Y	0.9369	likely_pathogenic	0.938	pathogenic	-0.836	Destabilizing	0.952	D	0.789	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.